title: Overexpression of a truncated growth hormone receptor in the sex-linked dwarf chicken: evidence for a splice mutation.
abstract: Sex-linked dwarfism in chickens is a form of GH resistance that resembles the Laron syndrome in humans. The dwarfism found in chickens is due to a mutant gene (dw) carried on the sex chromosome. The homozygous dwarf (dwdw) chicken is characterized by reductions in stature and plasma insulin-like growth factor-I (IGF-I) levels. Despite the absence of hepatic GH-binding activity, Southern blot analysis shows that there is no gross structural change in the gene for the GH receptor (GHR) in this strain of dwdw chicken. GH-dependent IGF-I production can be restored in cultured dwdw hepatocytes after transfection and transient expression of a chicken GHR (cGHR) cDNA, indicating that other factors that participate in GH-mediated IGF-I synthesis are intact. Northern blot analysis of liver, muscle, fat, and pituitary RNA from normal (DwDw) chickens shows a major transcript of 4.3 kilobases (kb) and three minor transcripts (0.8, 1.7, and 3.2 kb), which correspond to the cGHR. In contrast, the 0.8-kb transcript is the major cGHR transcript expressed in these tissues from dwdw chickens. Northern blot analysis with domain-specific probes shows that the 0.8-kb transcript in DwDw and dwdw liver contains only a small portion of the extracellular domain of the cGHR. A cDNA clone encoding this transcript has been isolated from a liver library prepared from a normal chicken.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Animal Science and Agricultural Biochemistry, College of Agricultural Sciences, University of Delaware, Newark 19717.
authors.forename: N
authors.initials: N
authors.lastname: Huang
authors.forename: L A
authors.initials: LA
authors.lastname: Cogburn
authors.forename: S K
authors.initials: SK
authors.lastname: Agarwal
authors.forename: H L
authors.initials: HL
authors.lastname: Marks
authors.forename: J
authors.initials: J
authors.lastname: Burnside
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002645:Chickens / Q000235:genetics*; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D004392:Dwarfism / Q000235:genetics / Q000662:veterinary*; D005786:Gene Expression Regulation; D005796:Genes; D005808:Genes, Recessive; D007334:Insulin-Like Growth Factor I / Q000172:deficiency*; D008099:Liver / Q000166:cytology; D008969:Molecular Sequence Data; D017354:Point Mutation; D011061:Poly A / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011201:Poultry Diseases / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011986:Receptors, Somatotropin / Q000172:deficiency* / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D012730:Sex Chromosomes; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D011061:Poly A; D007334:Insulin-Like Growth Factor I