RESUMO
Animal domestication has resulted in changes in growth and size. It has been suggested that this may have involved selection for differences in appetite. Divergent growth between chickens selected for egg laying or meat production is one such example. The neurons expressing AGRP and POMC in the basal hypothalamus are important components of appetite regulation, as are the satiety feedback pathways that carry information from the intestine, including CCK and its receptor CCKAR (CCK1 receptor). Using 16 generations of a cross between a fast and a relatively slow growing strain of chicken has identified a region on chromosome 4 downstream of the CCKAR gene, which is responsible for up to a 19% difference in body weight at 12 wk of age. Animals possessing the high-growth haplotype at the locus have lower expression of mRNA and immunoreactive CCKAR in the brain, intestine, and exocrine organs, which is correlated with increased levels of orexigenic AGRP in the hypothalamus. Animals with the high-growth haplotype are resistant to the anorectic effect of exogenously administered CCK, suggesting that their satiety set point has been altered. Comparison with traditional breeds shows that the high-growth haplotype has been present in the founders of modern meat-type strains and may have been selected early in domestication. This is the first dissection of the physiological consequences of a genetic locus for a quantitative trait that alters appetite and gives us an insight into the domestication of animals. This will allow elucidation of how differences in appetite occur in birds and also mammals.
Assuntos
Animais Domésticos , Peso Corporal/genética , Peso Corporal/fisiologia , Galinhas/genética , Galinhas/fisiologia , Crescimento/genética , Crescimento/fisiologia , Receptor de Colecistocinina A/biossíntese , Receptor de Colecistocinina A/fisiologia , Resposta de Saciedade/fisiologia , Proteína Relacionada com Agouti/biossíntese , Proteína Relacionada com Agouti/genética , Alelos , Animais , Química Encefálica/fisiologia , Cruzamentos Genéticos , Ingestão de Alimentos/genética , Ingestão de Alimentos/fisiologia , Feminino , Genótipo , Imuno-Histoquímica , Masculino , Polimorfismo de Nucleotídeo Único/genética , RNA/biossíntese , RNA/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Receptor de Colecistocinina A/genética , Distribuição Tecidual , Transcrição GênicaRESUMO
PURPOSE: To identify the locus responsible for rge (retinopathy globe enlarged) in chickens and further characterise the rge phenotype. METHODS: A colony of chickens carrying the rge mutation was rederived from a single heterozygous animal of the original line. The eyes of blind, heterozygous and normal birds were subjected to ophthalmic, morphometric and histopathological examination to confirm and extend published observations. DNA samples were obtained and subjected to a whole genome linkage search. RESULTS: From 138 classified backcross progeny, 56 birds were blind and 82 sighted. Heterozygous birds were indistinguishable from wild type, but homozygotes had sluggish or unresponsive pupils, posterior sub-capsular lens opacities and an atrophic pecten. The fundus appeared normal with no significant pigmentary disturbance, but axial length and eye weight were increased. Pathology revealed focal retinal lesions. Linkage analysis placed the rge locus in a small region of chicken chromosome 1. CONCLUSIONS: rge is a severe recessive retinal dystrophy in chickens, with associated globe enlargement. Linkage mapping has highlighted chicken chromosome 1 in a region most probably homologous to human chromosomes 7q31-35, 21q21 or 22q12-21. Candidate disease loci include RP10 (IMPDH1) and uncharacterised Ushers (USH1E) and glaucoma (GLC1F) loci.
Assuntos
Cegueira/veterinária , Galinhas/genética , Órbita/patologia , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/patologia , Degeneração Retiniana/veterinária , Animais , Cegueira/genética , Cegueira/patologia , Catarata/genética , Catarata/patologia , Catarata/veterinária , Mapeamento Cromossômico , Cromossomos/genética , DNA/análise , Modelos Animais de Doenças , Feminino , Genes Recessivos , Ligação Genética , Genótipo , Hipertrofia , Cristalino/patologia , Masculino , Mutação , Distúrbios Pupilares/genética , Distúrbios Pupilares/patologia , Distúrbios Pupilares/veterinária , Degeneração Retiniana/genética , Degeneração Retiniana/patologiaRESUMO
PURPOSE: To identify the locus responsible for the blind mutation rdd (retinal dysplasia and degeneration) in chickens and to further characterise the rdd phenotype. METHODS: The eyes of blind and sighted birds were subjected to ophthalmic, morphometric and histopathological examination to confirm and extend published observations. Electroretinography was used to determine age of onset. Birds were crossed to create pedigrees suitable for genetic mapping. DNA samples were obtained and subjected to a linkage search. RESULTS: Measurement of IOP, axial length, corneal diameter, and eye weight revealed no gross morphological changes in the rdd eye. However, on ophthalmic examination, rdd homozygotes have a sluggish pupillary response, atrophic pecten, and widespread pigmentary disturbance that becomes more pronounced with age. Older birds also have posterior subcapsular cataracts. At three weeks of age, homozygotes have a flat ERG indicating severe loss of visual function. Pathological examination shows thinning of the RPE, ONL, photoreceptors and INL, and attenuation of the ganglion cell layer. From 77 classified backcross progeny, 39 birds were blind and 38 sighted. The rdd mutation was shown to be sex-linked and not autosomal as previously described. Linkage analysis mapped the rdd locus to a small region of the chicken Z chromosome with homologies to human chromosomes 5q and 9p. CONCLUSIONS: Ophthalmic, histopathologic, and electrophysiological observations suggest rdd is similar to human recessive retinitis pigmentosa. Linkage mapping places rdd in a region homologous to human chromosomes 9p and 5q. Candidate disease genes or loci include PDE6A, WGN1, and USH2C. This is the first use of genetic mapping in a chicken model of human disease.
