RESUMEN
BACKGROUND: Between 2020 and 2022, eight calves in a Nebraska herd (composite Simmental, Red Angus, Gelbvieh) displayed exercise intolerance during forced activity. In some cases, the calves collapsed and did not recover. Available sire pedigrees contained a paternal ancestor within 2-4 generations in all affected calves. Pedigrees of the calves' dams were unavailable, however, the cows were ranch-raised and retained from prior breeding seasons, where bulls used for breeding occasionally had a common ancestor. Therefore, it was hypothesized that a de novo autosomal recessive variant was causative of exercise intolerance in these calves. RESULTS: A genome-wide association analysis utilizing SNP data from 6 affected calves and 715 herd mates, followed by whole-genome sequencing of 2 affected calves led to the identification of a variant in the gene PYGM (BTA29:g.42989581G > A). The variant, confirmed to be present in the skeletal muscle transcriptome, was predicted to produce a premature stop codon (p.Arg650*). The protein product of PYGM, myophosphorylase, breaks down glycogen in skeletal muscle. Glycogen concentrations were fluorometrically assayed as glucose residues demonstrating significantly elevated glycogen concentrations in affected calves compared to cattle carrying the variant and to wild-type controls. The absence of the PYGM protein product in skeletal muscle was confirmed by immunohistochemistry and label-free quantitative proteomics analysis; muscle degeneration was confirmed in biopsy and necropsy samples. Elevated skeletal muscle glycogen persisted after harvest, resulting in a high pH and dark-cutting beef, which is negatively perceived by consumers and results in an economic loss to the industry. Carriers of the variant did not exhibit differences in meat quality or any measures of animal well-being. CONCLUSIONS: Myophosphorylase deficiency poses welfare concerns for affected animals and negatively impacts the final product. The association of the recessive genotype with dark-cutting beef further demonstrates the importance of genetics to not only animal health but to the quality of their product. Although cattle heterozygous for the variant may not immediately affect the beef industry, identifying carriers will enable selection and breeding strategies to prevent the production of affected calves.
Asunto(s)
Estudio de Asociación del Genoma Completo , Glucógeno Fosforilasa de Forma Muscular , Animales , Bovinos , Femenino , Masculino , Enfermedades de los Bovinos/genética , Genes Recesivos , Glucógeno Fosforilasa de Forma Muscular/genética , Glucógeno Fosforilasa de Forma Muscular/deficiencia , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Linaje , Polimorfismo de Nucleótido Simple , Secuenciación Completa del GenomaRESUMEN
Bovine familial convulsions and ataxia (BFCA) is considered an autosomal dominant syndrome with incomplete penetrance. Nine Angus calves from the same herd were diagnosed with BFCA within days of birth. Necropsy revealed cerebellar and spinal cord lesions associated with the condition. Parentage testing confirmed that all affected calves had a common sire. The sire was then bred to 36 cows across two herds using artificial insemination, producing an additional 14 affected calves. The objective of this investigation was to identify hypothesized dominant genetic variation underlying the condition. Whole-genome sequencing was performed on the sire, six affected and seven unaffected paternal half-sibling calves and combined with data from 135 unrelated controls. The sire and five of the six affected calves were heterozygous for a nonsense variant (Chr7 g.12367906C>T, c.5073C>T, p.Arg1681*) in CACNA1A. The other affected calves (N = 8) were heterozygous for the variant but it was absent in the other unaffected calves (N = 7) and parents of the sire. This variant was also absent in sequence data from over 6500 other cattle obtained via public repositories and collaborator projects. The variant in CACNA1A is expressed in the cerebellum of the ataxic calves as detected in the transcriptome and was not differentially expressed compared with controls. The CACNA1A protein is part of a highly expressed cerebellar calcium voltage gated channel. The nonsense variant is proposed to cause haploinsufficiency, preventing proper transmission of neuronal signals through the channel and resulting in BFCA.
Asunto(s)
Ataxia , Canales de Calcio , Enfermedades de los Bovinos , Convulsiones , Animales , Bovinos/genética , Canales de Calcio/genética , Ataxia/veterinaria , Ataxia/genética , Enfermedades de los Bovinos/genética , Convulsiones/veterinaria , Convulsiones/genética , Masculino , Femenino , Secuenciación Completa del Genoma/veterinaria , Genes Dominantes , MutaciónRESUMEN
Thirteen American Hereford cattle were reported blind with presumed onset when ~12-mo-old. All blind cattle shared a common ancestor through both the maternal and paternal pedigrees, suggesting a recessive genetic origin. Given the pedigree relationships and novel phenotype, we characterized the ophthalmo-pathologic changes associated with blindness and identified the responsible gene variant. Ophthalmologic examinations of 5 blind cattle revealed retinal degeneration. Histologically, 2 blind cattle had loss of the retinal photoreceptor layer. Whole-genome sequencing (WGS) of 7 blind cattle and 9 unaffected relatives revealed a 1-bp frameshift deletion in ceroid lipofuscinosis neuronal 3 (CLN3; chr25 g.26043843del) for which the blind cattle were homozygous and their parents heterozygous. The identified variant in exon 16 of 17 is predicted to truncate the encoded protein (p. Pro369Argfs*8) battenin, which is involved in lysosomal function necessary for photoreceptor layer maintenance. Of 462 cattle genotyped, only blind cattle were homozygous for the deletion. A query of WGS data of > 5,800 animals further revealed that the variant was only observed in related Hereford cattle. Mutations in CLN3 are associated with human juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease, which results in early-onset retinal degeneration and lesions similar to those observed in our cases. Our data support the frameshift variant of CLN3 as causative of blindness in these Hereford cattle, and provide additional evidence of the role of this gene in retinal lesions, possibly as a model for human non-syndromic JNCL.
Asunto(s)
Enfermedades de los Bovinos , Degeneración Retiniana , Animales , Bovinos , Degeneración Retiniana/veterinaria , Degeneración Retiniana/genética , Degeneración Retiniana/patología , Enfermedades de los Bovinos/genética , Enfermedades de los Bovinos/patología , Femenino , Linaje , Masculino , Glicoproteínas de Membrana/genética , Lipofuscinosis Ceroideas Neuronales/veterinaria , Lipofuscinosis Ceroideas Neuronales/genética , Lipofuscinosis Ceroideas Neuronales/patología , Chaperonas Moleculares/genética , Mutación del Sistema de LecturaRESUMEN
A white calf, with minimal pigmented markings, was born to two registered Black Angus parents. Given the possibility of an unknown recessive or de novo dominant mutation, whole-genome sequencing was conducted on the trio of individuals. A 3-bp in-frame deletion in MITF was identified; this mutation was unique to the calf but identical to the delR217 variant reported in both humans and murine models of Waardenburg syndrome type 2A and Tietz syndrome. Given the coat color phenotype and identity of the mutation, our data support that this calf represents the first instance of this recurring MITF mutation in cattle.
Asunto(s)
Enfermedades de los Bovinos , Factor de Transcripción Asociado a Microftalmía , Animales , Bovinos/genética , Humanos , Ratones , Enfermedades de los Bovinos/genética , Sordera/genética , Sordera/veterinaria , Factor de Transcripción Asociado a Microftalmía/genética , Mutación , Fenotipo , Eliminación de Secuencia , Síndrome de Waardenburg/genética , Síndrome de Waardenburg/veterinariaRESUMEN
In spring 2020, six Hereford calves presented with congenital facial deformities attributed to a condition we termed mandibulofacial dysostosis (MD). Affected calves shared hallmark features of a variably shortened and/or asymmetric lower mandible and bilateral skin tags present 2-10 cm caudal to the commissure of the lips. Pedigree analysis revealed a single common ancestor shared by the sire and dam of each affected calf. Whole-genome sequencing (WGS) of 20 animals led to the discovery of a variant (Chr26 g. 14404993T>C) in Exon 3 of CYP26C1 associated with MD. This missense mutation (p.L188P), is located in an α helix of the protein, which the identified amino acid substitution is predicted to break. The implication of this mutation was further validated through genotyping 2 additional affected calves, 760 other Herefords, and by evaluation of available WGS data from over 2500 other individuals. Only the affected individuals were homozygous for the variant and all heterozygotes had at least one pedigree tie to the suspect founder. CYP26C1 plays a vital role in tissue-specific regulation of retinoic acid (RA) during embryonic development. Dysregulation of RA can result in teratogenesis by altering the endothelin-1 signaling pathway affecting the expression of Dlx genes, critical to mandibulofacial development. We postulate that this recessive missense mutation in CYP26C1 impacts the catalytic activity of the encoded enzyme, leading to excess RA resulting in the observed MD phenotype.
Asunto(s)
Región Branquial/embriología , Enfermedades de los Bovinos/genética , Familia 26 del Citocromo P450/genética , Disostosis Mandibulofacial/genética , Animales , Región Branquial/anomalías , Bovinos , Genoma/genética , Mutación Missense/genética , Linaje , Tretinoina/metabolismo , Secuenciación Completa del GenomaRESUMEN
Right-sided congestive heart failure (brisket disease) commonly occurs in cattle raised at elevations >2,500-3,500 m. We investigated clinical cases resembling brisket disease at a western Nebraska feedyard at a moderate altitude (1,369 m). Over a 15-mo period (2009-2010), we examined 17 cases (16 steers and 1 heifer), all purebred Angus. All animals had clinical right-sided heart failure: brisket and ventral abdominal edema, and severe chronic passive congestion of the liver. Gross examination confirmed right ventricular hypertrophy (left ventricle plus septum: right ventricle weight ratio mean: 1.33 vs. 2.8-4.0 reference interval). Microscopically, all 17 cases had interstitial fibrosis (mean score: 2.4 ± 0.8) and 6 had replacement fibrosis of the right ventricle, whereas 14 had interstitial fibrosis (mean score: 1.2 ± 0.2) and 0 had replacement fibrosis of the left ventricle. Lesions of arteriosclerosis were seen in 9 of 16 cases in 51 of 571 (8.9%) right ventricular coronary arteries, and in 10 of 16 cases in 52 of 366 (14.2%) left ventricular coronary arteries. The probability of coronary arteriosclerosis was greater in papillary ventricular muscle (OR = 11.3; p < 0.0001), left ventricle (OR = 4.8; p < 0.0001), and larger arteries (OR = 1.01; p < 0.0001). Pulmonary arteries and arterioles had lesions compatible with hypoxia-induced pulmonary hypertension. We hypothesize that moderate hypobaric conditions significantly contributed to disease in cattle genetically predisposed to hypoxia-induced pulmonary hypertension. Adiposity, coronary arteriosclerosis, and left ventricular fibrosis may have contributed to the condition; however, the cattle died prior to development of advanced obesity.
Asunto(s)
Altitud , Enfermedades de los Bovinos/diagnóstico , Insuficiencia Cardíaca/veterinaria , Obesidad/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/etiología , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/etiología , Vivienda para Animales , Masculino , Nebraska , Obesidad/complicaciones , Obesidad/epidemiologíaRESUMEN
A genetic disorder, osteogenesis imperfecta (OI) is broadly characterized by connective tissue abnormalities and bone fragility most commonly attributed to alterations in Type I collagen. Two Red Angus calves by the same sire presented with severe bone and dental fragility, blue sclera, and evidence of in utero fractures consistent with OI congenita. Comparative analyses with human cases suggested the OI in these calves most closely resembled that classified as OI Type II. Due to the phenotypic classification and shared paternity, a dominant, germ-line variant was hypothesized as causative although recessive genotypes were also considered due to a close relationship between the sire and dam of one calf. Whole-genome sequencing revealed the presence of a missense mutation in the alpha 1 chain of collagen Type I (COL1A1), for which both calves were heterozygous. The variant resulted in the substitution of a glycine residue with serine in the triple helical domain of the protein; in this region, glycine normally occupies every third position as is critical for correct formation of the Type I collagen molecule. Allele-specific amplification by droplet digital PCR further quantified the variant at a frequency of nearly 4.4% in the semen of the sire while it was absent in his blood, supporting the hypothesis of a de novo causative variant for which the germ line of the sire was mosaic. The identification of novel variants associated with unwanted phenotypes in livestock is critical as the high prolificacy of breeding stock has the potential to rapidly disseminate undesirable variation.
Asunto(s)
Enfermedades de los Bovinos/genética , Mutación de Línea Germinal , Osteogénesis Imperfecta/veterinaria , Alelos , Animales , Bovinos , Enfermedades de los Bovinos/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Femenino , Genes Dominantes , Masculino , Mutación Missense , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/metabolismo , Linaje , FenotipoRESUMEN
Bovine viral diarrhea virus (BVDV) is a pathogen in cattle and alpacas ( Vicugna pacos), causing acute and persistent BVDV infections. We characterized the effect of acute BVDV infection on the immune system of alpacas by determining lymphocyte subpopulations in peripheral blood and gut-associated lymphoid tissues (GALT) as well as serum interferon levels. Alpacas were experimentally infected with BVDV-1b (strain CO-06). Peripheral blood leukocytes were isolated at 0, 3, 6, and 9 d postinfection (dpi), and leukocytes of GALT at 9 dpi, and evaluated using flow cytometry. Serum interferon levels were determined daily. Flow cytometric analyses of peripheral blood leukocytes showed a significant decrease in CD4+, CD8+, and αß T-lymphocytes at 3 dpi. CD8+ lymphocytes were significantly increased, and activated lymphocytes were significantly decreased in the C3-stomach region in BVDV-infected alpacas. Serum interferon concentrations significantly increased in BVDV-infected alpacas at 3-6 dpi, peaking at 3 dpi. Our study confirms that BVDV can be a primary acute pathogen in alpacas and that it induces an interferon response and alters leukocyte subset populations. The changes in the proportion of T-lymphocytes during the early stages of BVDV infection may result in transient immunosuppression that may contribute to secondary bacterial and viral infections, similar to cattle.
Asunto(s)
Diarrea Mucosa Bovina Viral/virología , Camélidos del Nuevo Mundo , Virus de la Diarrea Viral Bovina Tipo 1/inmunología , Animales , Bovinos , Citocinas/sangre , Virus de la Diarrea Viral Bovina Tipo 1/clasificación , Virus de la Diarrea Viral Bovina Tipo 1/genética , Citometría de Flujo/veterinaria , Mucosa Intestinal/citología , Mucosa Intestinal/virología , Leucocitos/clasificación , Leucocitos/citologíaRESUMEN
It was hypothesized that acute postnatal Bovine viral diarrhea virus 1 (BVDV-1) infection leads to leukopenia and lymphoid depletion of gut-associated lymphoid tissues similar to acute disease in calves. The objectives of the current study were to characterize the pathologic effects, viremia, viral shedding, and viral antigen deposition in 6-24-month-old, acutely infected alpacas following experimental infection with noncytopathic BVDV-1 subgenotype 1b (BVDV C0-6). The BVDV-1 isolate was obtained from a cria with naturally occurring persistent infection. Lymphocytopenia occurred 3-7 days postinfection, with a 50% reduction in peripheral lymphocytes in infected alpacas. Depletion of B-cell populations in gut-associated lymphoid tissues was evident microscopically. Populations of T cells in parafollicular zones and in nodular aggregates along the superficial submucosa remained intact. The BVDV antigen was deposited most consistently in submucosal gastrointestinal aggregated lymphoid tissues of ileum, proximal colon, and stomach compartment three. Viral antigen was more variably evident in other lymphoid tissues. Antigen distribution correlated well with histologic lesions in gastrointestinal aggregated lymphoid tissues, confirming the role of virus in lymphoid depletion. Nasal shedding was detected in all challenged alpacas on day 6 and in 4 out of 12 challenged alpacas on day 9. Viremia was present as early as day 3, and present in all challenged alpacas on days 5, 6, 7, and 9 postchallenge. Lymphocytopenia and depletion of gastrointestinal aggregated lymphoid tissues associated with acute BVDV-1 infection likely results in immune compromise and is expected to exacerbate concurrent infections even though uncomplicated BVDV-1 infection was clinically unapparent.
Asunto(s)
Camélidos del Nuevo Mundo/virología , Virus de la Diarrea Viral Bovina Tipo 1/inmunología , Tejido Linfoide/virología , Infecciones por Pestivirus/veterinaria , Animales , Camélidos del Nuevo Mundo/inmunología , Virus de la Diarrea Viral Bovina Tipo 1/genética , Inmunohistoquímica/veterinaria , Tejido Linfoide/inmunología , Linfopenia/inmunología , Linfopenia/veterinaria , Linfopenia/virología , Infecciones por Pestivirus/inmunología , Infecciones por Pestivirus/virología , ARN Viral/química , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Viremia/inmunología , Viremia/veterinaria , Viremia/virología , Esparcimiento de Virus/inmunologíaRESUMEN
BACKGROUND: Osteopetrosis is a skeletal disorder of humans and animals characterized by the formation of overly dense bones, resulting from a deficiency in the number and/or function of bone-resorbing osteoclast cells. In cattle, osteopetrosis can either be induced during gestation by viral infection of the dam, or inherited as a recessive defect. Genetically affected calves are typically aborted late in gestation, display skull deformities and exhibit a marked reduction of osteoclasts. Although mutations in several genes are associated with osteopetrosis in humans and mice, the genetic basis of the cattle disorder was previously unknown. RESULTS: We have conducted a whole-genome association analysis to identify the mutation responsible for inherited osteopetrosis in Red Angus cattle. Analysis of >54,000 SNP genotypes for each of seven affected calves and nine control animals localized the defective gene to the telomeric end of bovine chromosome 4 (BTA4). Homozygosity analysis refined the interval to a 3.4-Mb region containing the SLC4A2 gene, encoding an anion exchanger protein necessary for proper osteoclast function. Examination of SLC4A2 from normal and affected animals revealed a approximately 2.8-kb deletion mutation in affected calves that encompasses exon 2 and nearly half of exon 3, predicted to prevent normal protein function. Analysis of RNA from a proven heterozygous individual confirmed the presence of transcripts lacking exons 2 and 3, in addition to normal transcripts. Genotyping of additional animals demonstrated complete concordance of the homozygous deletion genotype with the osteopetrosis phenotype. Histological examination of affected tissues revealed scarce, morphologically abnormal osteoclasts displaying evidence of apoptosis. CONCLUSIONS: These results indicate that a deletion mutation within bovine SLC4A2 is associated with osteopetrosis in Red Angus cattle. Loss of SLC4A2 function appears to induce premature cell death, and likely results in cytoplasmic alkalinization of osteoclasts which, in turn, may disrupt acidification of resorption lacunae.
Asunto(s)
Proteínas de Transporte de Anión/genética , Antiportadores/genética , Osteopetrosis/genética , Eliminación de Secuencia , Animales , Portador Sano/metabolismo , Portador Sano/patología , Bovinos , Antiportadores de Cloruro-Bicarbonato , Femenino , Sitios Genéticos/genética , Homocigoto , Humanos , Masculino , Ratones , Osteopetrosis/patología , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas SLC4ARESUMEN
OBJECTIVE: To characterize the influence of the viral protein N(pro) on virulence of bovine viral diarrhea virus (BVDV) and on type I interferon responses in calves. ANIMALS: 10 calves, 4 to 6 months of age. PROCEDURES: BVDV virulence and type I interferon responses of calves (n = 5) infected with a noncytopathic BVDV with a deleted N(pro) were compared with those of calves (5) infected with a noncytopathic BVDV with a functional N(pro). Rectal temperatures, clinical signs, platelet counts, and total and differential WBC counts were evaluted daily. Histologic examinations and immunohistochemical analyses of tissues were conducted to assess lesions and distribution of viral antigens, respectively. Serum type I interferon concentrations were determined. RESULTS: Calves infected with N(pro)-deleted BVDV developed leukopenia and lymphopenia, without developing increased rectal temperatures or lymphoid depletion of target lymphoid organs. There was minimal antigen deposition in lymphoid organs. Calves infected with N(pro) BVDV developed increased rectal temperatures, leukopenia, lymphopenia, and lymphoid depletion with marked BVDV antigen deposition in lymphatic tissues. Interferon type I responses were detected in both groups of calves. CONCLUSIONS AND CLINICAL RELEVANCE: Deletion of N(pro) resulted in attenuation of BVDV as evidenced by reduced virulence in calves, compared with BVDV with a functional N(pro). Deletion of N(pro) did not affect induction of type I interferon. The N(pro)-deleted BVDV mutant may represent a safe noncytopathic virus candidate for vaccine development.
Asunto(s)
Diarrea Mucosa Bovina Viral/inmunología , Enfermedades de los Bovinos/virología , Virus de la Diarrea Viral Bovina/patogenicidad , Interferón Tipo I/biosíntesis , Proteínas de la Nucleocápside/farmacología , Virulencia/efectos de los fármacos , Animales , Temperatura Corporal , Bovinos , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/patología , Virus de la Diarrea Viral Bovina/efectos de los fármacos , Eutanasia , Interferón Tipo I/sangre , Ganglios Linfáticos Agregados/patología , Vacunas Virales/inmunologíaRESUMEN
OBJECTIVE: To determine the prevalence of bovine viral diarrhea virus (BVDV)-infected alpaca herds in the United States and investigate factors associated with seropositive herd status and, subsequently, determine the proportion of animals within seropositive alpaca herds that are persistently infected (PI) carriers for BVDV, obtain information regarding previous herd exposure to BVDV, determine titers of anti-BVDV antibodies of dams, and ascertain whether individual seropositive crias had received supplemental colostrum at birth. DESIGN: Prevalence study. ANIMALS: 63 alpaca herds with >or= 12 registered female alpacas. PROCEDURES: 250 alpaca breeders were randomly selected from 562 eligible herds listed in the Alpaca Owner and Breeders Association membership directory and mailed a voluntary participation request. Sixty-three alpaca breeders participated in the study. From each herd, blood samples from >or= 4 crias were tested for BVDV, BVDV RNA, and serum neutralizing antibodies against BVDV. A region of the genome of BVDV recovered from PI crias was sequenced to determine genetic homology. RESULTS: Among the 63 herds, 16 (25.4%) had seropositive crias and 4 (6.3%) had PI crias. Infections in 3 of the 4 herds with PI crias were linked as evidence by the genetic homologies of viruses. In addition to PI crias, feeding supplemental colostrum was associated with herd seropositivity. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirmed the importance of BVDV infections in alpacas in the United States and highlighted the importance of determining the BVDV infection status of animals before they are commingled to limit exposure of herds to BVDV infection.
Asunto(s)
Diarrea Mucosa Bovina Viral/epidemiología , Camélidos del Nuevo Mundo/virología , Virus de la Diarrea Viral Bovina/aislamiento & purificación , Animales , Anticuerpos Antivirales/sangre , Secuencia de Bases , Portador Sano/epidemiología , Portador Sano/veterinaria , Bovinos , Calostro/virología , ADN Viral/química , ADN Viral/genética , Virus de la Diarrea Viral Bovina/inmunología , Femenino , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Estudios Seroepidemiológicos , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: To evaluate protection resulting from use of a modified-live noncytopathic bovine viral diarrhea virus (BVDV) type 1 vaccine against systemic infection and clinical disease in calves challenged with type 2 BVDV. ANIMALS: 10 calves, 5 to 7 months of age. PROCEDURES: Calves were allocated (n = 5/group) to be nonvaccinated or vaccinated SC on day 0 with BVDV 1 (WRL strain). Calves in both groups were challenged intranasally with BVDV type 2 isolate 890 on day 21. Rectal temperatures and clinical signs of disease were recorded daily, and total and differential WBC and platelet counts were performed. Histologic examinations and immunohistochemical analyses to detect lesions and distribution of viral antigens, respectively, were performed. RESULTS: After challenge exposure to BVDV type 2, nonvaccinated calves developed high rectal temperatures, increased respiratory rates, viremia, leukopenia, lymphopenia, and infection of the thymus. Vaccinated calves did not develop high rectal temperatures or clinical signs of respiratory tract disease. Vaccinated calves appeared to be protected against systemic replication of virus in that they did not develop leukopenia, lymphopenia, viremia, or infection of target organs, and infectious virus was not detected in peripheral blood mononuclear cells or the thymus. CONCLUSIONS AND CLINICAL RELEVANCE: The modified-live BVDV type 1 vaccine protected against systemic infection and disease after experimental challenge exposure with BVDV type 2. The vaccine protected calves against infection and viremia and prevented infection of target lymphoid cells.
Asunto(s)
Diarrea Mucosa Bovina Viral/inmunología , Diarrea Mucosa Bovina Viral/prevención & control , Virus de la Diarrea Viral Bovina Tipo 1/inmunología , Virus de la Diarrea Viral Bovina Tipo 2/inmunología , Vacunas Virales/inmunología , Vacunas Virales/uso terapéutico , Animales , Anticuerpos Antivirales/sangre , Variación Antigénica , Temperatura Corporal , Diarrea Mucosa Bovina Viral/virología , Bovinos , Reacciones Cruzadas , Inmunohistoquímica/veterinaria , Mucosa Nasal/virología , Pruebas de Neutralización/veterinaria , Timo/virología , Vacunación/veterinaria , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/uso terapéutico , Viremia/inmunología , Viremia/virología , Esparcimiento de Virus/inmunologíaRESUMEN
Mulefoot disease (MFD) is an autosomal recessive disorder of phenotypically variable expression that causes syndactyly in certain strains of cows. MFD maps to a narrow interval on bovine chromosome 15 that is syntenic to human chromosome 11p12-p11.2. This region contains MEGF7/LRP4 (approved gene symbol LRP4), a gene that encodes a member of the multifunctional low-density lipoprotein receptor gene family. Targeted and naturally occurring mutations in the murine Megf7/Lrp4 gene, a putative coreceptor in the Wnt signaling pathway, cause polysyndactyly in the rodent. Thus, Megf7/Lrp4 is a strong candidate for the MFD mutation. Using PCR analysis of tissue samples and sperm from confirmed homozygous MFD carriers, we have identified a functional single base pair mutation in the affected animals. We show that a G --> A transition at the first nucleotide in the splice donor site of intron 37 completely disables this splice site. The abnormal splicing that is caused by this mutation predicts the generation of a dysfunctional membrane-anchored receptor lacking the normal cytoplasmic domain. These findings confirm that autosomal recessive loss-of-function mutations in Megf7/Lrp4 result in phenotypically similar forms of syndactyly in different mammalian species and that such mutations are the cause of MFD in bovines.
Asunto(s)
Enfermedades de los Bovinos/genética , Bovinos/genética , Receptores de LDL/genética , Sindactilia/veterinaria , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Mapeo Cromosómico , ADN/genética , Extremidades/crecimiento & desarrollo , Genes Recesivos , Genómica , Humanos , Intrones , Proteínas Relacionadas con Receptor de LDL , Ratones , Datos de Secuencia Molecular , Empalme del ARN , Sindactilia/genética , Técnicas del Sistema de Dos HíbridosRESUMEN
A cross-sectional study was used to test the relationship between herd seroprevalence to Neospora caninum and various potential herd-level risk factors in 60 dairy farms located in two distinct regions in southern Brazil. Thirty farms were randomly selected from within each region. A questionnaire was designed to summarize each farm's production system as it might relate to N. caninum transmission. The questionnaire contained 105 closed questions relating to general characteristics of the farms, farm facilities, management, source of food and water, herd health, environment and biosecurity, which included questions relevant to N. caninum transmission, including presence and number of dogs and other animals, purchase of animals and contact with man. Serum samples were collected from 40% of animals in each farm and N. caninum antibodies were detected by immunofluorescent antibody test (IFAT). The association between potential risk factors and the probability of an animal being seropositive was modeled using a generalized estimation equations (GEE) logistic regression model. The model accounted for multilevel correlation of data from multiple animals within herds. The mean (+/-S.D.) number of animals in the 60 herds was 64.5 (+/-45.6), ranging from 20 to 280 females. Blood samples were collected from 1549 animals. The size of the farms varied from 4 to 100 ha (mean 30.1+/-25.9 ha). At least one dog was found in 57 of the 60 dairy farms (95%). The mean number of dogs was 3.1 (+/-1.9), ranging from 0 to 10. All females were raised on pasture. For all cattle sampled, N. caninum seroprevalence was 17.8%. Overall, 93.3% of herds (56/60) had at least one seropositive animal identified. Four variables were significantly associated with N. caninum sero-response in the 57 dairy farms, which were included in the final multivariable model: the number of dogs on the farm, farm area (hectares), feeding pooled sources of colostrum and region. The odds of a cow being seropositive increased 1.13 times for each additional dog present on the farm (P=0.021). Cattle from farms that fed calves colostrum pooled from multiple cows had 1.79 times greater odds for being seropositive for N. caninum (P<0.003). The probability of being seropositive was inverse to the area of the farms, such that cattle had 0.92 times the odds to be seropositive (P=0.014) for each additional 10 ha of farmland. Finally, cattle from farms in region one had 0.71 times the odds to be seropositive than cattle from region two (P=0.035). Results of this study suggest that several risk factors may explain why dairy cattle in Brazil may become exposed to N. caninum. However, further investigation of these factors is necessary because the purpose of this study was to refine and generate hypotheses on N. caninum transmission.
Asunto(s)
Aborto Espontáneo/etiología , Anticuerpos Antiprotozoarios/sangre , Enfermedades de los Bovinos/epidemiología , Coccidiosis/veterinaria , Neospora/inmunología , Animales , Brasil/epidemiología , Bovinos , Enfermedades de los Bovinos/parasitología , Enfermedades de los Bovinos/transmisión , Coccidiosis/epidemiología , Coccidiosis/transmisión , Estudios Transversales , Perros , Femenino , Fluoroinmunoensayo , Humanos , Modelos Logísticos , Factores de Riesgo , Estudios Seroepidemiológicos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To evaluate protection against systemic infection and clinical disease provided by use of a modified-live noncytopathic bovine viral diarrhea virus (BVDV) type 1 vaccine in calves challenged with NY-1 BVDV. ANIMALS: 10 calves, 5 to 7 months of age. PROCEDURES: Calves were allocated (n = 5/group) to be nonvaccinated or vaccinated SC on day 0 with BVDV type 1 (WRL strain). Calves in both groups were challenged intranasally with NY-1 BVDV on day 21. Calves' rectal temperatures and clinical signs of disease were recorded daily, total and differential WBC and platelet counts were performed, and serum neutralizing antibody titers against NY-1 BVDV were determined. Histologic examinations and immunohistochemical analyses to detect gross lesions and distribution of viral antigens, respectively, were performed. RESULTS: After challenge exposure to NY-1 BVDV, nonvaccinated calves developed high rectal temperatures, increased respiratory rates, viremia, leukopenia, lymphopenia, and infection of the thymus. Vaccinated calves did not develop high rectal temperatures or clinical signs of respiratory tract disease. Vaccinated calves appeared to be protected against systemic replication of virus in that they did not develop leukopenia, lymphopenia, viremia, or infection of target organs, and infectious virus was not detected in peripheral blood mononuclear cells or the thymus. CONCLUSIONS AND CLINICAL RELEVANCE: The modified-live BVDV vaccine protected calves against systemic infection and disease after experimental challenge exposure with NY-1 BVDV. The vaccine protected calves against infection and viremia and prevented infection of target lymphoid cells.
Asunto(s)
Diarrea Mucosa Bovina Viral/prevención & control , Virus de la Diarrea Viral Bovina Tipo 1/inmunología , Vacunas Virales/inmunología , Análisis de Varianza , Animales , Recuento de Células Sanguíneas , Temperatura Corporal , Bovinos , Virus de la Diarrea Viral Bovina Tipo 1/aislamiento & purificación , Inmunohistoquímica , Pruebas de Neutralización , Timo/virología , Viremia/prevención & control , Viremia/veterinaria , Esparcimiento de VirusRESUMEN
OBJECTIVE: To determine outcome of equids in the western United States with clinical signs of West Nile virus (WNV) infection and identify factors associated with risk of death in infected equids. DESIGN: Cross-sectional study. ANIMALS: 484 equids in Nebraska and Colorado. PROCEDURE: Owners of 484 equids with laboratory-confirmed West Nile virus infection in Nebraska and Colorado were contacted by telephone, and a questionnaire was used to obtain information on signalment, management, clinical signs, date of disease onset, duration of disease, WNV vaccination status, and health status at the time of the interview. RESULTS: 137 of 482 (28.4%) animals died or were euthanatized. Ataxia, lethargy, muscle fasciculations, and weakness were the most common clinical signs of disease. Animals > or = 3 years old were more likely to die than were animals < or = 2 years old. Unvaccinated equids were twice as likely to die as were animals that had been vaccinated at least once prior to the onset of disease. Animals that were recumbent and unable to rise were 78 times as likely to die as were animals that never lost the ability to rise. Females were 2.9 times as likely to die as males. Two hundred seventy-one of 339 (79.9%) animals that survived recovered fully; mean duration of disease for these animals was 22.3 days. CONCLUSIONS AND CLINICAL RELEVANCE: Among equids with WNV infection, age, vaccination status, an inability to rise, and sex were associated with the risk of death.
Asunto(s)
Enfermedades de los Caballos/mortalidad , Vacunación/veterinaria , Fiebre del Nilo Occidental/veterinaria , Virus del Nilo Occidental/patogenicidad , Factores de Edad , Crianza de Animales Domésticos/métodos , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Antivirales/uso terapéutico , Colorado/epidemiología , Estudios Transversales , Femenino , Enfermedades de los Caballos/tratamiento farmacológico , Caballos , Modelos Logísticos , Masculino , Nebraska/epidemiología , Factores de Riesgo , Factores Sexuales , Análisis de Supervivencia , Resultado del Tratamiento , Vacunación/estadística & datos numéricos , Fiebre del Nilo Occidental/tratamiento farmacológico , Fiebre del Nilo Occidental/mortalidadRESUMEN
OBJECTIVE: To determine the comparative virulence of 5 isolates of bovine viral diarrhea virus (BVDV) type II by inoculating 6- to 9-month-old beef calves with isolates originating from the tissues of cattle affected with naturally occurring, transient, acute, nonfatal infections or naturally occurring, peracute, fatal infections. ANIMALS: 22 calves that were 6 to 9 months old. PROCEDURE: The study used BVDV isolates 17011, 713, and 5521 that originated from fetuses aborted from cows with transient, nonfatal, acute BVDV infections and isolates 23025 and 17583 that originated from the tissues of cattle with peracute, fatal BVDV infections. Calves were allotted to 6 groups (1, mock-infected control calves [n = 2]; 2, inoculated with BVDV 17011 [4]; 3, inoculated with BVDV 713 [4]; 4, inoculated with BVDV 5521 [4]; 5, inoculated with BVDV 23025 [4]; and 6, inoculated with BVDV 17583 [41]. Rectal temperatures and clinical signs of disease were recorded daily. Total and differential WBC and platelet counts were performed. Histologic examination and immunohistochemical analysis were conducted to detect lesions and distribution of viral antigens, respectively. RESULTS: Calves inoculated with BVDV 23025 or 17583 developed more severe clinical signs of disease (fever and diarrhea), more severe lymphopenia, and more severe lesions (alimentary epithelial necrosis, lymphoid depletion, and BVDV antigen deposition in lymphatic tissues), compared with calves inoculated with BVDV 713, 5521, or 17011. CONCLUSIONS AND CLINICAL RELEVANCE: Relative severity of experimentally induced infections corresponded to severity of clinical signs of naturally occurring infections with respective BVDV isolates.
Asunto(s)
Diarrea Mucosa Bovina Viral/virología , Virus de la Diarrea Viral Bovina Tipo 2/clasificación , Virus de la Diarrea Viral Bovina Tipo 2/patogenicidad , Envejecimiento , Animales , Bovinos , Factores de Tiempo , VirulenciaRESUMEN
OBJECTIVE: To compare experimentally induced concurrent infection with bovine viral diarrhea virus (BVDV) and bovine rotavirus (BRV) with infection of either virus alone in calves. ANIMALS: Seventeen 1-day-old gnotobiotic calves. PROCEDURE: Calves were allotted to 8 treatments as follows: group 1, mock-infected control calves (n = 2); group 2, inoculated with BVDV on day 1 (2); groups 3, 5, and 7, inoculated with BRV on days 1 (2), 4 (1), or 7 (2), respectively; and groups 4, 6, and 8, inoculated with BVDV on day 1 and with BRV on days 1 (2), 4 (2), or 7 (4), respectively. Concentrations of BVDV in serum and ileal tissues were measured, and BRV shedding in feces was determined. Histologic examination and immunohistochemical analysis were conducted to detect lesions and viral antigens. RESULTS: Neonatal calves inoculated with BVDV alone or with BVDV on day 1 and BRV on day 7 developed villus atrophy and submucosal inflammation of the intestines. Concurrent BVDV and BRV infections acted synergistically in the intestinal tract, causing more severe enteric disease than infection with either virus alone. Severe lymphoid depletion was associated with BVDV infection in calves regardlesss of concurrent BRV infection. CONCLUSIONS AND CLINICAL RELEVANCE: Infection with BVDV played direct and indirect roles in enteritis in neonatal calves, causing villus atrophy in the duodenum and submucosal inflammation of the intestines. Also, BVDV potentiated effects of BRV. Concurrent infection with BVDV and BRV resulted in more severe enteric disease in neonatal calves than infection with BRV or BVDV alone.
Asunto(s)
Diarrea Mucosa Bovina Viral/complicaciones , Virus de la Diarrea Viral Bovina , Enteritis/veterinaria , Infecciones por Rotavirus/veterinaria , Rotavirus , Animales , Animales Recién Nacidos , Anticuerpos Antivirales/sangre , Antígenos Virales/metabolismo , Diarrea Mucosa Bovina Viral/sangre , Diarrea Mucosa Bovina Viral/virología , Bovinos , Virus de la Diarrea Viral Bovina/patogenicidad , Enteritis/patología , Enteritis/virología , Heces/virología , Íleon/patología , Íleon/virología , Inmunohistoquímica/veterinaria , Rotavirus/patogenicidad , Infecciones por Rotavirus/sangre , Infecciones por Rotavirus/complicaciones , Infecciones por Rotavirus/virología , Organismos Libres de Patógenos EspecíficosRESUMEN
A degenerative skeletal muscle disease with vascular, neurologic, and renal lesions and a probable familial distribution was identified in 4-20-month-old purebred Gelbvieh cattle. Thirteen affected animals were confirmed from 6 separate beef herds, with a mortality rate of 100%. Clinical signs in affected animals consisted of ataxia, weakness, and terminal recumbency. Gross and histologic muscle lesions were indicative of nutritional myopathy of ruminants, with a lack of myocardial lesions in most cases and only rare myocardial changes in a few animals. Acute to chronic lesions in most large skeletal muscle groups consisted of degeneration, necrosis, regeneration, fibrosis, and atrophy. Fibrinoid necrosis of arterioles was a common feature in multiple tissues. Lesions in the spinal cord white matter and peripheral nerves consisted of degeneration of the dorsal columns and axons, respectively. Changes in the kidneys consisted of chronic interstitial nephritis with fibrosis, hyaline droplet change and tubular epithelial vacuolar change and were most severe in the older calves. Intracytoplasmic myoglobin and iron were demonstrated within the hyaline droplets in degenerate renal cortical tubular epithelial cells. Vitamin E levels were deficient in most (6/7) of the animals tested. Investigation of the pedigree of affected animals revealed a common ancestry for all but 1 of the animals whose parentage could be traced. This investigation suggests that a hereditary metabolic defect, possibly involving antioxidant metabolism, could be responsible for this condition. Renal disease, possibly secondary to myoglobinuria, may be unique to this bovine condition.