Abnormal growth hormone receptor gene expression in the sex-linked dwarf chicken

Abstract

Sex-finked dwarfism is a recessive mutation that causes a reduction in body weight gain and long bone growth of chickens. We examined the effect of the dwarfing gene on body weight, hepatic GH-binding activity, and the structure and expression of the growth hormone receptor (GHR) gene in two different lines of sex-linked dwarf (SLD) broiler chickens. Liver samples from one line of dwarf chicken were obtained from Arbor Acres Farm, Inc. (Glastonbury, CT) and fertile eggs from the second line of SLD were obtained from the University of Georgia. In the GA line, the average body weight of homozygous ( dwdw) males at 1 1 weeks of age was 43% lower than that of normal ( DwDw) males, while heterozygous ( Dwdw) males were only 9% below normal. In the CT fine, hepatic GH-binding activity of 35-week-old chickens was high (20% specific binding) in normal ( DwDw) males and undetectable in liver membranes prepared from dwdw males. At 11 weeks of age, hepatic GH-binding activity of Dwdw males (3.9% specific binding) in the GA line was reduced by 44% and that of dwdw males was almost undetectable (0.34% specific binding) when compared to the average of normal GA males (7.l%-specific binding). Southern and Northern blot analyses revealed different abnormalities in the GHR.. gene from the two separate lines of SLD. A restriction fragment length polymorphism in DNA and an aberrantly sized transcript (mRNA) were detected in the CT line of SLD chickens. In the GA line, the DNA restriction pattern of dwdw males was identical to that found in normal GA chickens; however, there was no expression of the GHR gene in dwdw chickens since we did not detect an mRNA that corresponds to the GHR. These data suggest that the molecular defect of SLD chickens resides within the gene for the GHR and the dwdw phenotype results from a lack of synthesis of a functional GHR protein.