Overexpression of a truncated growth hormone receptor in the sex-linked dwarf chicken: evidence for a splice mutation

Mol Endocrinol. 1993 Nov;7(11):1391-8. doi: 10.1210/mend.7.11.8114754.

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)

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cells, Cultured
  • Chickens / genetics*
  • DNA Mutational Analysis
  • DNA, Complementary / genetics
  • Disease Models, Animal*
  • Dwarfism / genetics
  • Dwarfism / veterinary*
  • Gene Expression Regulation*
  • Genes
  • Genes, Recessive
  • Insulin-Like Growth Factor I / deficiency*
  • Liver / cytology
  • Molecular Sequence Data
  • Point Mutation*
  • Poly A / metabolism
  • Polymerase Chain Reaction
  • Poultry Diseases / genetics*
  • RNA Splicing*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Receptors, Somatotropin / deficiency*
  • Receptors, Somatotropin / genetics
  • Regulatory Sequences, Nucleic Acid
  • Sex Chromosomes*
  • Transfection

Substances

  • DNA, Complementary
  • RNA, Messenger
  • Receptors, Somatotropin
  • Poly A
  • Insulin-Like Growth Factor I