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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Molecular cloning of the chicken growth hormone receptor complementary deoxyribonucleic acid: mutation of the gene in sex-linked dwarf chickens.

A novel complementary DNA (cDNA) encoding the chicken GH receptor was isolated from a chicken liver cDNA library, using polymerase chain reaction with primers derived from highly conserved sequences of the mammalian GH receptor. The nucleotide sequence predicts a mature protein of 592 amino acids and a 16 amino acid signal peptide that are partially homologous to the sequence reported for the rabbit (53%), rat (58%), and human (50%) GH receptors. Despite this low level of homology, a number of structural features of the GH receptor are conserved, including 7 cysteine residues in the extracellular domain and 5 in the intracellular region. Three transcripts of approximately 4.7, 4.0, and 1.0 kilobases are present on Northern blots of total RNA prepared from the livers of 35-week-old male chickens. Expression of the GH receptor was also detected in a wide range of tissues. The chicken GH receptor cDNA was then used as a probe in Southern and Northern blot analyses of DNA and RNA prepared from livers of sex-linked dwarf chickens, which have undetectable levels of hepatic GH-binding activity, in addition to other endocrine abnormalities. A restriction fragment length polymorphism was found in DNA, and an aberrantly-sized transcript was found in hepatic RNA of the dwarf chicken. These results indicate that a mutation in the GH receptor gene is responsible for the phenotype of the sex-linked dwarf chicken. This type of dwarfism resembles Laron-type dwarfism in humans, where a defect in the GH receptor gene has recently been identified. These receptor-deficient chickens should serve as a unique model system for studying the role of the GH receptor in growth and development.[1]


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