RESUMO
A minority of patients with nonsyndromic autosomal recessive congenital ichthyosis (ARCI) display mutations in NIPAL4 (ICHTHYIN). This protein plays a role in epidermal lipid metabolism, although the mechanism is unknown. The study describes a moderate form of ARCI in an extended pedigree of American Bulldogs that is linked to the gene encoding ichthyin. The gross phenotype was manifest as a disheveled pelage shortly after birth, generalized scaling, and adherent brown scale with erythema of the abdominal skin. Pedigree analysis indicated an autosomal recessive mode of inheritance. Ultrastructurally, the epidermis showed discontinuous lipid bilayers, unprocessed lipid within corneocytes, and abnormal lamellar bodies. Linkage analysis, performed by choosing simple sequence repeat markers and single-nucleotide polymorphisms near genes known to cause ACRI, revealed an association with NIPAL4. NIPAL4 was identified and sequenced using standard methods. No mutation was identified within the gene, but affected dogs had a SINE element 5' upstream of exon 1 in a highly conserved region. Of 545 DNA samples from American Bulldogs, 32 dogs (17 females, 15 males) were homozygous for the polymerase chain reaction fragment. All affected dogs were homozygous, with parents heterozygous for the insertion. Immunolabeling revealed an absence of ichthyin in the epidermis. This is the first description of ARCI associated with decreased expression of NIPAL4 in nonhuman species.
Assuntos
Ictiose Lamelar/genética , Receptores de Superfície Celular/genética , Animais , Modelos Animais de Doenças , Cães , Epiderme/patologia , Feminino , Homozigoto , Ictiose Lamelar/patologia , Metabolismo dos Lipídeos , Masculino , Mutagênese Insercional , Linhagem , Fenótipo , Receptores de Superfície Celular/metabolismo , Pele/patologiaRESUMO
A 3-year-old African fat-tail gecko (Hemitheconyx caudicinctus) suddenly became lethargic and died 2 days later. Necropsy examination revealed a submandibular mass and discolouration of the liver, kidneys and skeletal muscles of the tail. Microscopical evaluation revealed neoplastic mast cells in the skin, liver, kidneys, skeletal muscles, bones, spleen, uterus, ovaries and lungs. Exfoliative cytological, histopathological and ultrastructural features were consistent with systemic mastocytosis. Neoplastic proliferative disorders of mast cells are rare in reptiles and this is the first report of mast cell neoplasia in geckos.
Assuntos
Mastocitose Sistêmica/veterinária , Animais , Feminino , Lagartos , Mastócitos/patologia , Mastocitose Sistêmica/patologiaRESUMO
BACKGROUND: Congenital, nonepidermolytic cornification disorders phenotypically resembling human autosomal recessive ichthyosis have been described in purebred dog breeds, including Jack Russell terrier (JRT) dogs. One cause of gene mutation important to humans and dogs is transposon insertions. OBJECTIVES: To describe an autosomal recessive, severe nonepidermolytic ichthyosis resembling lamellar ichthyosis (LI) in JRT dogs due to insertion of a long interspersed nucleotide element (LINE-1) in the transglutaminase 1 (TGM1) gene. METHODS: Dogs were evaluated clinically, and skin samples were examined by light and electron microscopy. Phenotypic information and genotyping with a canine microsatellite marker suggested TGM1 to be a candidate gene. Genomic DNA samples and cDNA generated from epidermal RNA were examined. Consequences of the mutation were evaluated by Western blotting, quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme activity from cultured keratinocytes. RESULTS: Affected dogs had generalized severe hyperkeratosis. Histological examination defined laminated to compact hyperkeratosis without epidermolysis; ultrastructurally, cornified envelopes were thin. Affected dogs were homozygous for a 1980-bp insertion within intron 9 of TGM1. The sequence of the insertion was that of a canine LINE-1 element. Quantitative RT-PCR indicated a significant decrease in TGM1 mRNA in affected dogs compared with wild-type. TGM1 protein was markedly decreased on immunoblotting, and membrane-associated enzyme activity was diminished in affected dogs. CONCLUSIONS: Based on morphological and molecular features, this disease is homologous with TGM1-deficient LI in humans, clinically models LI better than the genetically modified mouse and represents its first spontaneous animal model. This is the first reported form of LI due to transposon insertion.
Assuntos
Doenças do Cão/genética , Ictiose Lamelar/veterinária , Elementos Nucleotídeos Longos e Dispersos/genética , Mutagênese Insercional/genética , Transglutaminases/genética , Animais , Biópsia/veterinária , Elementos de DNA Transponíveis/genética , Doenças do Cão/patologia , Cães , Feminino , Marcadores Genéticos , Ictiose Lamelar/genética , Ictiose Lamelar/patologia , Imuno-Histoquímica , Íntrons/genética , Masculino , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Pele/patologia , Especificidade da Espécie , Transglutaminases/deficiência , Transglutaminases/metabolismoRESUMO
A scaling disorder specific to Golden Retriever dogs has been recognized by both dermatologists and pathologists, but to date has not been well characterized. At the University of Pennsylvania's Laboratory of Toxicology and Pathology, 46 cases of ichthyosis were diagnosed histologically in Golden Retriever dogs from January 2004 to January 2007. A total of 22 dogs had skin lesions documented at younger than 1 year of age; 3 dogs between 1 and 2 years of age; 13 dogs developed lesions at older than 2 years; and the time of onset was unknown for 8 dogs. A total of 25 dogs were female, and 21 were male. All dogs had strikingly similar histopathologic changes that consisted of mild to moderate laminar orthokeratotic hyperkeratosis with an absence of epidermal hyperplasia and dermal inflammation. Ultrastructural analysis using a ruthenium tetroxide fixation method was performed on punch biopsy samples from 5 dogs and compared with 2 control dogs (1 clinically and histologically normal sibling of an affected dog and 1 Cairn Terrier). All affected dogs had retained and convoluted membranes with crystalline structures in the stratum corneum. Scattered keratinocytes in the granular cell layer had prominent, clear, membrane-bound, cytoplasmic vacuoles. Pedigree analysis of 14 dogs was compatible with autosomal recessive inheritance, but incomplete dominance could not be ruled out. This unique hyperkeratotic/scaling disorder in Golden Retrievers has distinctive clinical, histologic, and ultrastructural features, which are consistent with a primary cornification defect.
Assuntos
Doenças do Cão/patologia , Ictiose/veterinária , Animais , Biópsia por Agulha/veterinária , Doenças do Cão/genética , Cães , Feminino , Histocitoquímica/veterinária , Ictiose/genética , Ictiose/patologia , Masculino , Microscopia Eletrônica de Transmissão/veterinária , Linhagem , Estudos RetrospectivosRESUMO
BACKGROUND: Epidermolytic hyperkeratosis in humans is caused by dominant-negative mutations in suprabasal epidermal keratins 1 and 10. However, spontaneous keratin mutations have not been confirmed in a species other than human. OBJECTIVES: To describe an autosomal recessive, mild, nonpalmar/plantar epidermolytic ichthyosis segregating in an extended pedigree of Norfolk terrier dogs due to a splice-site mutation in the gene encoding keratin 10 (KRT10). METHODS: Dogs were evaluated clinically, and skin samples were examined by light and electron microscopy. Genomic DNA samples and cDNA from skin RNA were sequenced and defined a mutation in KRT10. Consequences of the mutation were evaluated by assessing protein expression with immunohistochemistry and Western blotting and gene expression with real-time RT-PCR (reverse transcriptase-polymerase chain reaction). RESULTS: Adult dogs with the disease had generalized, pigmented hyperkeratosis with epidermal fragility. Light microscopic examination defined epidermolysis with hyperkeratosis; ultrastructural changes included a decrease in tonofilaments and abnormal filament aggregation in upper spinous and granular layer keratinocytes. Affected dogs were homozygous for a single base GT-->TT change in the consensus donor splice site of intron 5 in KRT10. Keratin 10 protein was not detected with immunoblotting in affected dogs. Heterozygous dogs were normal based on clinical and histological appearance and keratin 10 protein expression. The mutation caused activation of at least three cryptic or alternative splice sites. Use of the cryptic sites resulted in transcripts containing premature termination codons. One transcript could result in shortening of the proximal portion of the 2B domain before the stutter region. Quantitative real-time PCR indicated a significant decrease in KRT10 mRNA levels in affected dogs compared with wild-type dogs. CONCLUSIONS: This disease is the first confirmed spontaneous keratin mutation in a nonhuman species and is the first reported recessive form of epidermolytic hyperkeratosis.
Assuntos
Doenças do Cão/genética , Hiperceratose Epidermolítica/veterinária , Queratinas/genética , Mutação Puntual , Animais , Doenças do Cão/metabolismo , Doenças do Cão/patologia , Cães , Feminino , Expressão Gênica , Genes Recessivos , Hiperceratose Epidermolítica/genética , Hiperceratose Epidermolítica/metabolismo , Hiperceratose Epidermolítica/patologia , Queratina-10 , Queratinas/metabolismo , Masculino , Linhagem , Sítios de Splice de RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Pele/metabolismoRESUMO
In order to extend knowledge of the process of cornification across species and to be better able to recognize inborn errors in keratin synthesis in the dog, we describe the organization and chromosome mapping of canine KRT1 and KRT2E and compare these results to human and murine sequence data. The coding regions of KRT1 and KRT2E are 1,860 bp and 1,902 bp respectively, distributed over nine exons. Both genes are localized on the canine radiation hybrid map to chromosome 27 in the type II keratin gene cluster close to polymorphic markers. These genes are highly conserved across species and based on both genomic and amino acid sequences, canine KRT1 and KRT2E share greater homology with humans than with mice.
Assuntos
Queratinas/genética , Mapeamento de Híbridos Radioativos/métodos , Análise de Sequência de DNA/métodos , Animais , Cães , Humanos , Camundongos , Dados de Sequência Molecular , Peptídeos/química , Estrutura Terciária de Proteína/genética , Análise de Sequência de Proteína/métodos , Análise de Sequência de Proteína/estatística & dados numéricosRESUMO
Although well-characterized in man, abnormal cornification secondary to heritable superficial keratin defects is rarely reported in animals. This report describes a mild cornification defect in seven related Norfolk terrier dogs. Lesions were present at birth and pedigree analysis suggested an autosomal recessive mode of inheritance. The affected dogs had hyperpigmented skin with scaling following mild trauma. The lesions were generalized but most prominent in the glabrous skin of the axillary and inguinal regions-areas where the epidermis is not protected by hair and is subject to frequent trauma. The most striking histological change was vacuolation in the upper epidermis, which often resulted in epidermolysis and blister formation. All of the affected dogs showed similar gross and histological changes. Ultrastructural changes included abnormal keratin filament clumping, prominent clear spaces in the cytoplasm of suprabasal keratinocytes, and abnormal keratohyaline granules. Immunohistochemical labelling for keratin 10 demonstrated a lack of expression in the superficial epidermis of affected dogs. All of the morphological changes noted in the Norfolk terriers were consistent with a mild form of a heritable defect in superficial keratin synthesis.
Assuntos
Epiderme/patologia , Queratinas/deficiência , Dermatopatias/genética , Dermatopatias/veterinária , Animais , Cães , Epiderme/ultraestrutura , Feminino , Imuno-Histoquímica , Queratina-10 , Masculino , Microscopia Eletrônica , LinhagemRESUMO
There is incredible morphological and behavioral diversity among the hundreds of breeds of the domestic dog, CANIS FAMILIARIS. Many of these breeds have come into existence within the last few hundred years. While there are obvious phenotypic differences among breeds, there is marked interbreed genetic homogeneity. Thus, study of canine genetics and genomics is of importance to comparative genomics, evolutionary biology and study of human hereditary diseases. The most recent version of the map of the canine genome is comprised of 3,270 markers mapped to 3,021 unique positions with an average intermarker distance of approximately 1 Mb. The markers include approximately 1,600 microsatellite markers, about 1,000 gene-based markers, and almost 700 bacterial artificial chromosome-end markers. Importantly, integration of radiation hybrid and linkage maps has greatly enhanced the utility of the map. Additionally, mapping the genome has led directly to characterization of microsatellite markers ideal for whole genome linkage scans. Thus, workers are now able to exploit the canine genome for a wide variety of genetic studies. Finally, the decision to sequence the canine genome highlights the dog's evolutionary and physiologic position between the mouse and human and its importance as a model for study of mammalian genetics and human hereditary diseases.
Assuntos
Cães/genética , Genoma , Animais , Evolução Molecular , HumanosRESUMO
The transglutaminase 1 gene (TGM1) encodes an enzyme necessary for cross-linking the structural proteins that form the cornified envelope, an essential component of the outermost layer of the skin, the stratum corneum. Reported here is the complete coding region of canine TGM1, its chromosome localization, and its map position in the integrated canine linkage-radiation hybrid map. Canine TGM1 consists of 2,448 nucleotides distributed over 15 exons. The nucleotide sequence has 90% identity to human TGM1. The deduced canine TGM1 protein is 816 amino acids long and is 92% identical to human TGM1. Using fluorescence in situ hybridization, we localized canine TGM1 to dog (Canis familiaris) chromosome 8 (CFA 8q). Canine TGM1 localized to CFA 8 on the integrated linkage-radiation hybrid map in the interval FH2149-MYH7. Characterizing the coding region of canine TGM1 is a first step in examining the role of this enzyme in normal and defective cornification in the dog.
Assuntos
Doenças do Cão/genética , Mapeamento Físico do Cromossomo , Transglutaminases/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Doenças do Cão/enzimologia , Cães , Éxons/genética , Ligação Genética/genética , Humanos , Hibridização in Situ Fluorescente , Íntrons/genética , Dados de Sequência Molecular , Mapeamento de Híbridos Radioativos , Alinhamento de Sequência , Análise de Sequência de DNA , Dermatopatias/enzimologia , Dermatopatias/genética , Dermatopatias/veterináriaRESUMO
The effects of hypothyroidism on canine skin were determined by comparing morphologic, morphometric, and hair cycle differences in skin biopsy samples from 3 groups of age- and gender-matched Beagle dogs: (1) euthyroid dogs; (2) dogs made hypothyroid by administration of 131I; and (3) dogs made hypothyroid and maintained in a euthyroid state by treatment with synthetic thyroxine. After 10 months of observation, there was slower regrowth of hair 2 months after clipping in the untreated-hypothyroid dogs. Untreated-hypothyroid dogs had a greater number of follicles in telogen and fewer hair shafts (ie, a greater number of hairless telogen follicles) than did the control group. The control dogs had a greater number of telogen follicles but the same number of hair shafts as the treated-hypothyroid group. Treated-hypothyroid dogs had the greatest number of follicles in the growing stage of the hair cycle (anagen). This study suggests that, at least in Beagles, induced hypothyroidism does not affect the pelage as dramatically as has been described in naturally occurring disease. This is because normal Beagles retain hair shafts in follicles for long periods, and the alopecia of hypothyroidism appears to evolve slowly because of the prolongation of this haired telogen stage. The evaluation of thyroxine-treated hypothyroid dogs demonstrates that thyroid hormone supplementation of Beagle dogs with induced hypothyroidism stimulates hair growth.
Assuntos
Alopecia/veterinária , Doenças do Cão/patologia , Folículo Piloso/patologia , Hipotireoidismo/veterinária , Tiroxina/farmacologia , Alopecia/etiologia , Animais , Cães , Folículo Piloso/efeitos dos fármacos , Hipotireoidismo/complicações , MasculinoRESUMO
Ninety-seven pure-bred Akitas were examined clinically and histologically for sebaceous adenitis. The diagnosis was established histologically in 23 Akitas by demonstrating an inflammatory reaction targeted against the sebaceous glands or a reduction in the number of glands. The clinical course of sebaceous adenitis in the Akita was similar to that seen in other breeds. The first skin lesions occurred mainly on the dorsal midline and ears. Compared with the Poodle, the age at first onset of the disease was more variable and the hair loss affected mainly the undercoat. The progression of sebaceous gland destruction varied between dogs and was not seen in all cases. Because bud-like sebaceous gland proliferation could be identified, it seems that regeneration of the sebaceous glands may occur. An autosomal recessive inheritance appears to be possible. Apart from a genetic background, immune-mediated factors possibly influence the onset and course of sebaceous adenitis.
Assuntos
Doenças do Cão/epidemiologia , Doenças do Cão/patologia , Linfadenite/veterinária , Doenças das Glândulas Sebáceas/veterinária , Animais , Dorso , Cruzamento , Doenças do Cão/genética , Cães , Orelha , Feminino , Predisposição Genética para Doença , Linfadenite/epidemiologia , Linfadenite/patologia , Masculino , Linhagem , Doenças das Glândulas Sebáceas/epidemiologia , Doenças das Glândulas Sebáceas/patologia , Texas/epidemiologiaRESUMO
A severe myopathy leading to death or euthanasia was identified in 4 Belgian and 4 Percheron draught horses age 2-21 years. Clinical signs ranged from overt weakness and muscle atrophy in 2 horses age 2 and 3 years, to recumbency with inability to rise in 6 horses age 4-21 years. In 5 horses there was mild to severe increases in muscle enzyme levels. Clinical diagnoses included equine motor neuron disease (2 horses), post anaesthetic myopathy (2 horses), exertional myopathy (2 horses), myopathy due to unknown (one horse), and equine protozoal myelitis (one horse). Characteristic histopathology of muscle from affected horses was the presence of excessive complex polysaccharide and/or glycogen, revealed by periodic acid-Schiff staining in all cases and by electron microscopy in one case. Evaluation of frozen section histochemistry performed on 2 cases indicated that affected fibres were Type 2 glycolytic fibres. Subsarcolemmal and intracytoplasmic vacuoles were most prominent in 3 horses age 2-4 years, and excessive glycogen, with little or no complex polysaccharide, was the primary compound stored in affected muscle in these young horses. Myopathic changes, including fibre size variation, fibre hypertrophy, internal nuclei, and interstitial fat infiltration, were most prominent in 5 horses age 6-21 years, and the accumulation of complex polysaccharide appeared to increase with age. Mild to moderate segmental myofibre necrosis was present in all cases.
Assuntos
Doença de Depósito de Glicogênio/veterinária , Doenças dos Cavalos/metabolismo , Doenças Musculares/veterinária , Polissacarídeos/metabolismo , Animais , Atrofia , Feminino , Glicogênio/metabolismo , Doença de Depósito de Glicogênio/complicações , Doença de Depósito de Glicogênio/metabolismo , Doença de Depósito de Glicogênio/patologia , Histocitoquímica , Doenças dos Cavalos/patologia , Cavalos , Hipertrofia , Masculino , Microscopia Eletrônica de Transmissão e Varredura , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Doenças Musculares/etiologia , Doenças Musculares/metabolismo , Doenças Musculares/patologia , NecroseRESUMO
An 8-year-old Trakehner mare developed fulminant pulmonary edema following suspected upper airway obstruction 50 minutes into an otherwise unremarkable anesthetic recovery after surgery for left cricoarytenoideus dorsalis muscle reinnervation and ventriculocordectomy. Establishing a patent airway by orotracheal reintubation and cardiopulmonary resuscitation attempts were unsuccessful. Gross, histological, and electron microscopic postmortem examination showed severe hemorrhagic pulmonary edema. Laryngeal swelling or hemorrhage were not evident, suggesting laryngospasm or functional airway collapse associated with the underlying left laryngeal paralysis, as a cause of the upper airway obstruction. Negative pressure pulmonary edema is rarely reported in the veterinary literature as a postanesthetic complication.
Assuntos
Obstrução das Vias Respiratórias/veterinária , Período de Recuperação da Anestesia , Doenças dos Cavalos/etiologia , Doenças dos Cavalos/fisiopatologia , Cavalos/fisiologia , Edema Pulmonar/veterinária , Obstrução das Vias Respiratórias/complicações , Obstrução das Vias Respiratórias/fisiopatologia , Animais , Feminino , Doenças dos Cavalos/patologia , Pulmão/patologia , Pulmão/fisiopatologia , Pulmão/ultraestrutura , Microscopia Eletrônica/veterinária , Respiração com Pressão Positiva , Edema Pulmonar/etiologia , Edema Pulmonar/fisiopatologiaRESUMO
The biochemical holding strength and histological characteristics of a laparoscopic stapled gastropexy (LG) adhesion were compared with that of an incisional gastropexy (IG) adhesion. An LG was performed in 14 dogs and an IG was performed in six dogs. During the LG procedure, the abdomen was insufflated with carbon dioxide and three cannulae were placed in the caudal aspect of the right side of the abdomen. A 35 mm laparoscopic stapler was used to staple the gastric antrum to the adjacent right lateral abdominal wall. The IG procedure was performed through ventral midline celiotomy. A 35 mm IG was made by apposing the gastric antrum to the adjacent right lateral abdominal wall with two continuous rows of suture. Half of each group of dogs was euthanatized at 7 and 30 days after surgery. The mean tensile load to failure at 7 days was 44.86 +/- 18.54 N for the LG group and 85.33 +/- 23.59 N for the IG group (P < .05). At 30 days the values were 72.39 +/- 18.01 N for the LG group and 71.17 +/-12.11 N for the IG group (P = .41). The gastropexy adhesions in the 7-day postoperative group contained variable amounts of fibrin, hemorrhage, mononuclear cell inflammation, loose fibrovascular tissue, and mature collagenous connective tissue. Adhesions in the 7-day postoperative group were divided subjectively into three histological subgroups based on the relative amounts of mature connective tissue within the adhesion. The LG and IG adhesions were randomly distributed among these subgroups (P = 1.0). Adhesions in the 30-day postoperative group contained well-organized fibrous connective tissue. No difference in the amount of connective tissue could be detected histologically in the LG or IG adhesions. Complications with the LG procedure included stomach perforation (2 cases), splenic puncture (2 cases), and subcutaneous emphysema (4 cases).
Assuntos
Cães/cirurgia , Laparoscopia/veterinária , Estômago/cirurgia , Animais , Fenômenos Biomecânicos , Doenças do Cão/prevenção & controle , Doenças do Cão/cirurgia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Volvo Gástrico/prevenção & controle , Volvo Gástrico/cirurgia , Volvo Gástrico/veterinária , Resultado do TratamentoRESUMO
Based on microscopic examination of the brains of seven wild-caught nurse sharks (Ginglymostoma cirratum), we observed a severe meningoencephalitis associated with numerous parasitic granulomas. The parasites were larval nematodes with morphological characteristics of the Superfamily Dracunculoidea. Although meningeal larval aggregates were associated with chronic inflammation, additional parasitic nodules found on the endocardial surface and perimandibular region did not provoke an inflammatory response. Neither the route of infection nor life cycle were determined.