A novel phenotype for Laron dwarfism in miniature Bos indicus cattle suggests that the expression of growth hormone receptor 1A in liver is required for normal growth

Mutations within the growth hormone receptor (GHR) gene that lead to an ina ctivated or truncated GHR protein cause abnormal growth and small adult siz e in a variety of species (Laron dwarfism). We studied a line of miniature Bos indicus cattle that have phenotypic (small mature size) and endocrine ( increased blood growth hormone and decreased blood insulin-like growth fact or-I concentrations) similarities to Laron dwarfs. Liver mRNA from miniatur e and control cattle was used to amplify a cDNA within the coding region of the GHR. The miniature cattle had GHR mRNA size (determined by Northern bl ot) and cDNA sequence that were similar to control cattle and, therefore, w ere unlike most Laron dwarf genotypes in which the GHR gene is mutated. Amo unts of mRNA from liver as well as muscle (superficial neck and longissimus ) were analyzed by ribonuclease protection assay for IGF-I, total GHR, GHR 1A (inducible, liver-specific GHR mRNA), and GHR 1B (constitutive GHR mRNA) , Four control and five miniature bulls were tested. As expected, liver IGF -I mRNA was decreased in the miniature cattle (approximately 12% of control ; P < 0.01). The amount of the total GHR as well, as GHR 1A mRNA were also decreased in liver (17% and 19% of control, respectively; P < 0.01). Other GHR mRNA, including GHR 1B mRNA, were similar for miniature and control cat tle. In muscle, there was a tendency (P < 0.10) for decreased IGF-I mRNA an d increased GHR mRNA in miniature compared with control cattle. In summary, a novel phenotype for Laron dwarfism in Bos indicus cattle was associated with underexpression of GHR 1A mRNA, but not other GHR mRNA variants in liv er. In addition to decreased GHR 1A mRNA, the miniature cattle had decrease d liver IGF-I mRNA. Full expression of GHR 1A in liver, therefore, may be r equired for full liver TGF-I expression and normal growth. (C) 1999 Elsevie r Science Inc. All rights reserved.