RESUMEN
C-C chemokine receptor 5 (CCR5) plays an essential role in HIV pathogenesis as the major coreceptor on CD4+ T cells used by HIV, yet the function of CCR5 on CD8 T cells is not well understood. Furthermore, the immunologic effects of the CCR5 inhibitor maraviroc (MVC), despite approval for clinical use, have not yet been well evaluated for their potential effects on cytotoxic T-cell responses. In this study, we characterized the development and function of CCR5+CD8+ T cells in rhesus macaques with or without Simian immunodeficiency virus (SIV) infection. We also investigated the effects of the CCR5 antagonist MVC on functional CCR5+CD8+ T-cell responses in vitro. The data show that CCR5+CD8+ T cells have an effector memory phenotype and increase with age in systemic and mucosal lymphoid tissues as a heterogeneous population of polyfunctional CD8 T cells. In addition, CCR5 is highly expressed on SIV gag-specific (CM9+) CD8+ T cells in SIV-infected macaques, yet CCR5+CD8+ T cells are significantly reduced in mucosal lymphoid tissues with disease progression. Furthermore, in vitro MVC treatment reduced activation and cytokine secretion of CD8+ T cells via a CCR5-independent pathway. These findings suggest that surface CCR5 protein plays an important role in differentiation and activation of CD8+ T cells. Although MVC may be helpful in reducing chronic inflammation and activation, it may also inhibit virus-specific CD8+ T-cell responses. Thus optimal use of CCR5 antagonists either alone or in combination with other drugs should be defined by further investigation.-Wang, X., Russell-Lodrigue, K. E., Ratterree, M. S., Veazey, R. S., Xu, H. Chemokine receptor CCR5 correlates with functional CD8+ T cells in SIV-infected macaques and the potential effects of maraviroc on T-cell activation.
Asunto(s)
Antagonistas de los Receptores CCR5/farmacología , Linfocitos T CD8-positivos/inmunología , Activación de Linfocitos , Maraviroc/farmacología , Receptores CCR5/metabolismo , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Animales , Linfocitos T CD8-positivos/efectos de los fármacos , Células Cultivadas , Humanos , Células Jurkat , Macaca mulattaRESUMEN
Germinal center (GC) CD4+ follicular Th (Tfh) cells are critical for cognate B cell help in humoral immune responses to pathogenic infections. Although Tfh cells are expanded or depleted in HIV/SIV-infected adults, the effects of pediatric HIV/SIV infection on Tfh cells remain unclear. In this study, we examined changes in lymphoid follicle formation in lymph nodes focusing on GC Tfh cells, B cell development, and differentiation in SIV-infected neonatal rhesus macaques (Macaca mulatta) compared with age-matched cohorts. Our data showed that follicles and GCs of normal infants rapidly formed in the first few weeks of age, in parallel with increasing GC Tfh cells in various lymphoid tissues. In contrast, GC development and GC Tfh cells were markedly impaired in SIV-infected infants. There was a very low frequency of GC Tfh cells throughout SIV infection in neonates and subsequent infants, accompanied by high viremia, reduction of B cell proliferation/resting memory B cells, and displayed proinflammatory unresponsiveness. These findings indicate neonatal HIV/SIV infection compromises the development of GC Tfh cells, likely contributing to ineffective Ab responses, high viremia, and eventually rapid disease progression to AIDS.
Asunto(s)
Linfocitos B/inmunología , Centro Germinal/inmunología , Infecciones por VIH/inmunología , VIH/inmunología , Ganglios Linfáticos/inmunología , Macaca mulatta/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/fisiología , Linfocitos T Colaboradores-Inductores/inmunología , Animales , Animales Recién Nacidos , Diferenciación Celular , Proliferación Celular , Modelos Animales de Enfermedad , Humanos , Inmunidad Humoral , Memoria Inmunológica , Activación de Linfocitos , Comunicación Paracrina , ViremiaRESUMEN
BACKGROUND: Our previous study suggested newborns have competent immune systems with the potential to respond to foreign antigens and vaccines. In this study, we examined infant immune responses to tetanus toxoid (TT) vaccination in the presence of maternal antibody to TT. METHODS: We examined changes in plasma levels of tetanus toxoid-specific IgG1 (anti-TT IgG1) in a total of eight infant rhesus macaques from birth through 6 months of age using a commercial Monkey Anti-TT IgG1 ELISA kit. RESULTS: A significant correlation between anti-TT IgG1 levels in vaccinated dams and their paired newborn infants was detected in control (non-vaccinated) infants as previously reported. Maternal anti-TT IgG1 levels declined rapidly within 1 month of birth in non-vaccinated infants (n=4). In four infants vaccinated with TT at birth, we found two had rapid and robust antibody responses to vaccination. Interestingly, the other two first showed declining TT antibody levels for 2 weeks followed by increasing levels without additional vaccine boosts, indicating all four had good antibody responses to primary TT vaccination at birth, despite the presence of high levels of maternal antibodies to TT in all four infants. CONCLUSIONS: Our data indicate that newborn macaques have competent immune systems that are capable of generating their own primary antibody responses to vaccination, at least to tetanus antigens. Maternal antibodies thus do not significantly impair antibody response to the vaccination, even when received on the day of birth in infant rhesus macaques.
Asunto(s)
Anticuerpos Antibacterianos/inmunología , Bordetella pertussis/inmunología , Inmunidad Materno-Adquirida/inmunología , Inmunoglobulina G/inmunología , Macaca mulatta/inmunología , Toxoide Tetánico/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Autoantígenos/sangre , Autoantígenos/inmunología , Femenino , Inmunoglobulina G/sangre , VacunaciónRESUMEN
Impairment of the intestinal mucosal immune system is an early feature of HIV-infected children. Most infected children exhibit clinical gastrointestinal symptoms at some stage of infection, and persistent diarrhea is a marker for rapid disease progression. It is known that Tregs are especially important in mediating intestinal immune homeostasis and that loss of this subset may result in intestinal inflammation and associated clinical signs. Large numbers of FoxP3(+) T cells were found in all tissues in newborn macaques, which coexpressed high levels of CD25 and CD4, indicating that they were Tregs. Moreover, neonates had much greater percentages of Tregs in intestinal tissues compared with peripheral lymphoid tissues. After SIV infection, a significant loss of Tregs was detected in the intestine compared with age-matched normal infants. Finally, SIV-infected FoxP3(+) T cells were detected in tissues in neonates as early as 7 SIV dpi. These results demonstrate that Tregs constitute a significant fraction of CD4(+) T cells in neonatal intestinal tissues and that an early, profound loss of Tregs occurs in acute SIV infection, which may contribute to the intestinal disorders associated with neonatal HIV infection.
Asunto(s)
Enfermedades Intestinales/inmunología , Intestinos/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/inmunología , Linfocitos T Reguladores/inmunología , Enfermedad Aguda , Animales , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/patología , VIH-1/inmunología , Humanos , Enfermedades Intestinales/etiología , Enfermedades Intestinales/patología , Intestinos/patología , Macaca mulatta , Masculino , Síndrome de Inmunodeficiencia Adquirida del Simio/complicaciones , Síndrome de Inmunodeficiencia Adquirida del Simio/patología , Linfocitos T Reguladores/patologíaRESUMEN
[This corrects the article on p. e29914 in vol. 7.].
RESUMEN
The persistence of symptoms in Lyme disease patients following antibiotic therapy, and their causes, continue to be a matter of intense controversy. The studies presented here explore antibiotic efficacy using nonhuman primates. Rhesus macaques were infected with B. burgdorferi and a portion received aggressive antibiotic therapy 4-6 months later. Multiple methods were utilized for detection of residual organisms, including the feeding of lab-reared ticks on monkeys (xenodiagnosis), culture, immunofluorescence and PCR. Antibody responses to the B. burgdorferi-specific C6 diagnostic peptide were measured longitudinally and declined in all treated animals. B. burgdorferi antigen, DNA and RNA were detected in the tissues of treated animals. Finally, small numbers of intact spirochetes were recovered by xenodiagnosis from treated monkeys. These results demonstrate that B. burgdorferi can withstand antibiotic treatment, administered post-dissemination, in a primate host. Though B. burgdorferi is not known to possess resistance mechanisms and is susceptible to the standard antibiotics (doxycycline, ceftriaxone) in vitro, it appears to become tolerant post-dissemination in the primate host. This finding raises important questions about the pathogenicity of antibiotic-tolerant persisters and whether or not they can contribute to symptoms post-treatment.
Asunto(s)
Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Borrelia burgdorferi/efectos de los fármacos , Enfermedad de Lyme/tratamiento farmacológico , Enfermedad de Lyme/microbiología , Macaca mulatta/microbiología , Animales , Formación de Anticuerpos/efectos de los fármacos , Formación de Anticuerpos/inmunología , ADN Bacteriano/análisis , ADN Bacteriano/genética , Inflamación/complicaciones , Inflamación/microbiología , Inflamación/patología , Enfermedad de Lyme/complicaciones , Enfermedad de Lyme/patología , Macaca mulatta/inmunología , Péptidos/inmunología , Resultado del Tratamiento , XenodiagnósticoRESUMEN
Globoid cell leukodystrophy, or Krabbe's disease, is a severe disorder of the central and peripheral nervous system caused by the absence of galactocerebrosidase (GALC) activity. Herein, we describe the clinical, neuropathological, histochemical, and immunohistological features observed in rhesus macaques affected with Krabbe's disease. Clinical signs included pronounced muscle tremors of head and limbs, difficulty ambulating, ataxia, hypermetria, proprioceptive deficits, and respiratory abnormalities. Histopathologically, all animals presented with evidence of demyelination in the peripheral and central nervous systems and accumulation of mononuclear and multinuclear globoid cells in the cerebral and cerebellar white matter associated with severe gliosis. Using immunohistochemistry and multi-label confocal microscopy, it was determined that globoid cells were CD68+, HAM56+, LN5+, CD163+, IBA-1+, and Glut-5+, suggesting that both peripheral blood-derived monocytes/macrophages and resident parenchymal microglia gave rise to globoid cells. Interestingly, many of the globoid cells and parenchymal microglia with a more ameboid morphology expressed HLA-DR, indicating immune activation. Increased expression of iNOS, TNF-alpha, and IL-1 beta were observed in the affected white matter, colocalizing with globoid cells, activated microglia, and astrocytes. Cytokine mRNA levels revealed markedly increased gene expression of CCL2 in the brain of affected macaques. CCL2-expressing cells were detected throughout the affected white matter, colocalizing with GFAP+ cells and astrocytes. Collectively, these data suggest that dysregulation of monocyte/macrophage/microglia and up-regulation of certain cytokines may contribute to the pathogenesis of Krabbe's disease.
Asunto(s)
Leucodistrofia de Células Globoides/diagnóstico , Leucodistrofia de Células Globoides/inmunología , Animales , Anticuerpos Monoclonales/biosíntesis , Antígenos CD/biosíntesis , Antígenos de Diferenciación Mielomonocítica/biosíntesis , Citocinas/metabolismo , Modelos Animales de Enfermedad , Galactosilceramidasa , Transportador de Glucosa de Tipo 5/biosíntesis , Antígenos HLA-DR/metabolismo , Sistema Inmunológico , Inmunohistoquímica/métodos , Macaca mulatta , Complejo Mayor de Histocompatibilidad , Monocitos/metabolismo , Receptores de Superficie Celular/biosíntesisRESUMEN
Krabbe disease is a progressive leukodystrophy that results in demyelination in the central and peripheral nervous systems in humans. It has been described in a number of mammalian species including the rhesus monkey. We performed serial nerve conduction studies beginning within the first 2 months of life in four homozygous, two heterozygous, and two normal rhesus monkeys (Macaca mulatta) to characterize the peripheral neuropathy. Mean conduction velocities of the median, ulnar, and tibial nerves were significantly slower in the affected than unaffected monkeys at all ages (P < 0.0001). The conduction velocity differences became more apparent between the affected and unaffected as the monkeys aged. When compared to the unaffected monkeys, the serial conduction velocities suggested occurrence of dysmyelination followed by demyelination in the affected monkeys. These observations provide further insight into the disease process and suggest an early window of opportunity for treating Krabbe disease.
Asunto(s)
Electrodiagnóstico , Leucodistrofia de Células Globoides/complicaciones , Leucodistrofia de Células Globoides/fisiopatología , Nervios Periféricos/fisiopatología , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Potenciales de Acción/fisiología , Factores de Edad , Envejecimiento/fisiología , Animales , Enfermedades Desmielinizantes/diagnóstico , Enfermedades Desmielinizantes/etiología , Enfermedades Desmielinizantes/fisiopatología , Macaca mulatta , Nervio Mediano/fisiopatología , Fibras Nerviosas Mielínicas/patología , Conducción Nerviosa/fisiología , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Nervio Tibial/fisiopatología , Nervio Cubital/fisiopatologíaRESUMEN
A study was conducted to assess the possibility of using pigtailed macaques (Macaca nemestrina) as recipients for rhesus macaque (Macaca mulatta) embryos. A total of 250 oocytes were collected from 11 rhesus monkeys during 12 follicular aspirations. We performed 15 embryo transfers with two embryos each into rhesus recipients, which resulted in eight pregnancies, of which two were lost during the second trimester. Among the remaining six pregnant rhesus macaques, two were carrying twins, resulting in the birth of eight infants. Twelve transfers of rhesus embryos into pigtailed macaques resulted in one pregnancy and the birth of one infant. Fetal growth and development were monitored by monthly ultrasound examinations, during which biparietal measurements were taken and compared with those derived from 22 pregnant control monkeys. In vitro fertilization-derived singletons tended to develop faster than did twins and naturally conceived control singletons during the initial months of pregnancy and weighed more at birth than did twins. There were pronounced morphologic changes in the placenta of the rhesus that developed in the female pigtailed macaque. These included an irregular shape, elevated placenta-to-birth-weight ratio, and an abnormal length and diameter of the umbilical cord. Histologic analyses of the rhesus-pigtailed placenta showed evidence of maternal-placental floor infarction and thrombosis of the spiral artery with resulting infarction of the villi. These results demonstrate that pigtailed macaques can carry rhesus fetuses to term, but further studies are necessary to determine the cause of the decreased pregnancy rates and observed placental abnormalities.
Asunto(s)
Transferencia de Embrión/veterinaria , Fertilización In Vitro/veterinaria , Desarrollo Fetal/fisiología , Macaca mulatta , Macaca nemestrina , Resultado del Embarazo/veterinaria , Animales , Estudios de Factibilidad , Femenino , Fertilización In Vitro/métodos , Placenta/patología , Embarazo , Índice de Embarazo , Especificidad de la EspecieRESUMEN
The availability of ChimeriVax vaccine technology for delivery of flavivirus protective antigens at the time West Nile (WN) virus was first detected in North America in 1999 contributed to the rapid development of the vaccine candidate against WN virus described here. ChimeriVax-Japanese encephalitis (JE), the first live- attenuated vaccine developed with this technology has successfully undergone phase I and II clinical trials. The ChimeriVax technology utilizes yellow fever virus (YF) 17D vaccine strain capsid and nonstructural genes to deliver the envelope gene of other flaviviruses as live-attenuated chimeric viruses. Amino acid sequence homology between the envelope protein (E) of JE and WN viruses facilitated targeting attenuating mutation sites to develop the WN vaccine. Here we discuss preclinical studies with the ChimeriVax-WN virus in mice and macaques. ChimeriVax-WN virus vaccine is less neurovirulent than the commercial YF 17D vaccine in mice and nonhuman primates. Attenuation of the virus is determined by the chimeric nature of the construct containing attenuating mutations in the YF 17D virus backbone and three point mutations introduced to alter residues 107, 316, and 440 in the WN virus E protein gene. The safety, immunogenicity, and efficacy of the ChimeriVax-WN(02) vaccine in the macaque model indicate the vaccine candidate is expected to be safe and immunogenic for humans.
Asunto(s)
Vacunas Sintéticas/inmunología , Vacunas Virales/inmunología , Virus del Nilo Occidental/inmunología , Virus de la Fiebre Amarilla/inmunología , Animales , Secuencia de Bases , Quimera , Chlorocebus aethiops , Femenino , Macaca fascicularis , Macaca mulatta , Ratones , Ratones Endogámicos ICR , Datos de Secuencia Molecular , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/inmunología , Células Vero , Vacunas Virales/efectos adversos , Virulencia , Virus del Nilo Occidental/genética , Virus de la Fiebre Amarilla/genéticaRESUMEN
Leptin is a polypeptide hormone produced by adipose and other endocrine tissues. Although it has been linked to receptor-mediated pathways that directly influence human conceptus development, mechanisms that regulate the leptin receptor in pregnancy-specific tissues remain unclear. Therefore, we assessed leptin-receptor ontogeny and regulation in the baboon (Papio sp.), a primate model for human pregnancy. Placentae, decidua, and amniochorion were collected from baboons in early (Days 54-63, n = 4), mid (Days 98-103, n = 4), and late (Days 159-165, n = 4) gestation. Regulation by estrogen was assessed by elimination of androgen precursors via removal of the fetus (fetectomy) at midgestation and collection of tissues in late gestation (n = 4; term, approximately 184 days). Maternal serum was sampled with advancing gestation, and the abundance of soluble leptin receptor (solLepR), a potential mediator of gestational hyperleptinemia, was determined. Two placental leptin-receptor isoforms (130 and 150 kDa) increased (P < 0.04 and P < 0.02, respectively) in abundance with advancing gestation. Similarly, the 130-kDa isoform increased approximately fourfold (P < 0.0025) in decidua and approximately 10-fold (P < 0.015) in amniochorion between early and late gestation. Following fetectomy, maternal serum estradiol levels declined approximately 85% (P < 0.03), and the 150-kDa placental leptin-receptor isoform was reduced by more than half (P < 0.002). Maternal serum solLepR concentrations were correlated with gestational age (r = 0.52, P < 0.01) and were unaffected by fetectomy. The presence of leptin-receptor isoforms in pregnancy-specific tissues further denoted leptin's potential to directly influence conceptus development, whereas the 130-kDa solLepR identified in maternal serum suggested a means to facilitate the hyperleptinemia typical of primate pregnancy. Although estrogen did not appear to be the principal regulator of solLepR, it and other factors linked to advancing gestation may be implicated in the regulation of leptin-receptor synthesis.
Asunto(s)
Edad Gestacional , Papio/metabolismo , Preñez/metabolismo , Receptores de Superficie Celular/química , Receptores de Superficie Celular/metabolismo , Animales , Disponibilidad Biológica , Estrógenos/sangre , Femenino , Papio/sangre , Embarazo , Preñez/sangre , Isoformas de Proteínas/metabolismo , Receptores de Superficie Celular/biosíntesis , Receptores de Superficie Celular/sangre , Receptores de Leptina , SolubilidadRESUMEN
Serological diagnosis of West Nile virus (WNV) infection is complicated by extensive antigenic cross-reactivity with other closely related flaviviruses, such as St. Louis encephalitis virus. Here we describe a recombinant, bacterially expressed antigen equivalent to structural domain III of the WNV envelope protein that has allowed clear discrimination of antibody responses to WNV from those against other related flaviviruses in indirect enzyme-linked immunosorbent assays using standardized control antisera and field-collected samples.
Asunto(s)
Anticuerpos Antivirales/sangre , Antígenos Virales/inmunología , Fiebre del Nilo Occidental/diagnóstico , Virus del Nilo Occidental/inmunología , Animales , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina G/sangre , Ratones , Subunidades de Proteína , Conejos , Proteínas Recombinantes/inmunología , Pruebas SerológicasRESUMEN
Reports of transfusion-associated cases of West Nile virus (WNV) infection indicate the need for sensitive screening methods to identify WNV-infected blood products. We experimentally infected 5 rhesus macaques with WNV, to determine the level and duration of viremia, the kinetics of the humoral immune response, and the sensitivity of various assay systems for detecting WNV in blood. All macaques developed subclinical infections with low levels of viremia; nested reverse-transcription polymerase chain reaction was the most sensitive method for detecting virus or viral RNA in blood. Specific WNV antibodies appeared during the second week of infection; the results of an IgM enzyme-linked immunosorbent assay became positive on the ninth or tenth day after infection, followed in 1-2 days by hemagglutination-inhibiting and neutralizing antibodies. Our results suggest that both nucleic acid and serological testing may be needed to determine exposure to WNV and to identify potentially infected blood donors.
Asunto(s)
Anticuerpos Antivirales/sangre , Viremia/fisiopatología , Fiebre del Nilo Occidental/fisiopatología , Virus del Nilo Occidental/aislamiento & purificación , Animales , Formación de Anticuerpos , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Pruebas de Inhibición de Hemaglutinación , Inmunoglobulina M/sangre , Macaca mulatta , Masculino , ARN Viral/sangre , ARN Viral/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Viremia/sangre , Viremia/inmunología , Fiebre del Nilo Occidental/sangre , Fiebre del Nilo Occidental/inmunología , Virus del Nilo Occidental/genéticaRESUMEN
During the summer of 2002, an epidemic of West Nile meningoencephalitis occurred in southern Louisiana. Following the outbreak, blood samples were collected from 1,692 captive rhesus monkeys (Macaca mulatta), pigtail macaques (M. nemestrina), and baboons (Papio spp.) that were permanently housed outdoors at a nonhuman primate breeding facility in St. Tammany Parish, Louisiana. The serum samples were examined for antibodies to West Nile virus (WNV). Overall, 36% of the captive nonhuman primates had WNV antibodies; comparison of these samples with banked serum samples from previous blood collections indicated that the animals were infected subclinically from February to August 2002. WNV activity was demonstrated in surveillance at the nonhuman primate-breeding colony and in the neighboring community during this same period. The high infection rate in this captive nonhuman primate population illustrates the intensity of WNV transmission that can occur silently in nature among other susceptible vertebrates during epidemic periods.
Asunto(s)
Anticuerpos Antivirales/sangre , Brotes de Enfermedades/veterinaria , Enfermedades de los Primates/epidemiología , Fiebre del Nilo Occidental/veterinaria , Virus del Nilo Occidental/inmunología , Crianza de Animales Domésticos , Animales , Humanos , Louisiana/epidemiología , Macaca mulatta , Macaca nemestrina , Papio , Prevalencia , Enfermedades de los Primates/virología , Fiebre del Nilo Occidental/epidemiología , Virus del Nilo Occidental/patogenicidadRESUMEN
OBJECTIVE: To determine the effects of chilling on the organization and distribution of tubulin and chromosomes in rhesus monkey oocytes. DESIGN: Comparative laboratory study. SETTING: Academic research laboratory. ANIMAL(S): Eight adult female rhesus monkeys (Macaca mulatta) aged 6-16 years. INTERVENTION(S): A total of 171 oocytes retrieved from eight rhesus monkeys were separated into nine groups. One group of control oocytes was held at 37 degrees C during the experiment. Four groups of oocytes were rapidly cooled to 0 degrees C and held for 1, 5, 10, or 30 minutes and then fixed and stained. Four other groups of oocytes were cooled to 0 degrees C, held for 1, 5, 10, or 30 minutes, warmed and incubated at 37 degrees C for 60 minutes, and then fixed and stained. MAIN OUTCOME MEASURE(S): Organization of cytoskeleton and chromosomes. RESULT(S): Exposure of rhesus oocytes to 0 degrees C for only 1 minute resulted in complete depolymerization of tubulin. Incubation of chilled oocytes at 37 degrees C for 60 minutes caused partial restoration of tubulin, although most oocytes exhibited abnormal alignment of chromosomes and disorganized meiotic spindles. CONCLUSION(S): We conclude that rhesus monkey oocytes are extremely sensitive to chilling injury. Their successful cryopreservation may require rapid cooling to outpace this injury.
Asunto(s)
Cromosomas/ultraestructura , Frío , Macaca mulatta , Oocitos/ultraestructura , Tubulina (Proteína)/ultraestructura , Animales , Femenino , Meiosis , Oocitos/química , Polímeros , Factores de Tiempo , Tubulina (Proteína)/análisisRESUMEN
Atrichia with papular lesions (APL) is a rare form of hair loss with an autosomal recessive mode of inheritance that is characterized by the absence of normal hair follicles, and formation of intradermal cystic structures. Mutations in the hairless (hr) gene in mice and humans have been implicated in the development of this phenotype. Hairless is a putative transcription factor containing a single zinc-finger DNA binding domain, with restricted expression in brain and skin. Here, we describe the complete hr cDNA sequence from the rhesus macaque (Macaca mulatta) and report the identification of a compound heterozygous mutation in a hairless rhesus macaque born from unrelated parents. Cutaneous biopsy samples from the affected macaque revealed abnormalities, including the replacement of normal hair follicles with dermal cysts and comedones, reminiscent of the skin phenotype observed in hairless mice and humans with APL.