The little (lit) mutation cosegregates with the growth hormone releasing factor receptor on mouse Chromosome 6

✍ Scribed by Streamson C. Chua; Karen Hennessey; Phillip Zeitler; Rudolph L. Leibel

• Publisher: Springer-Verlag
• Year: 1993
• Tongue: English
• Weight: 529 KB
• Volume: 4
• Category: Article
• ISSN: 0938-8990
• DOI: 10.1007/bf00361384

✦ Synopsis

The little (lit) autosomal recessive mutation in the mouse causes dwarfism due to isolated growth hormone deficiency. The in vitro physiology of pituitary growth hormone release in lit~lit animals suggests that an abnormality in the growth hormone releasing factor (GRF) receptor (Ghrfr) is a very likely candidate for the lit mutation. We mapped Ghrfr to the region around lit on Chromosome (Chr) 6 in 100 chromosomes of an FVB • Czech II interspecific backcross.

Molecular markers were Neuropeptide Y (Npy), homeobox (Hoxa2), immunoglobulin kappa chain (Igk), wingless-related MMTV integration site (Wnt-2), cystic fibrosis (Cftr), carboxypeptidase A (Cpa), and Ghrfr. Map order and distances were as follows: Cen-//-Wnt-2-(O cM)-Cftr-(6.0 cM)-Cpa-(8.0 cM)-Npy-(1.0 cM)-Hoxa2-(3.0 cM)-Ghrfr-(2.0 cM)-Igk. We mapped lit (by phenotype) relative to Hoxa2 and Igk on 72 F2 chromosomes of offspring of a B6CZ lit~ + x B6FVB lit~ + intercross and 18 chromosomes of offspring of a B6FVB lit~ + intercross. Map order and distances were as follows: Hoxa2-(2.1 cM)-lit/Ghrfr-(3.7 cM)-lgk. No recombinations between lit and Ghrfr were detected. Thus, Ghrfr maps to mouse Chr 6 and may be allelic with lit. Amplification of a short segment at the 3' end of the Ghrfr mRNA by reverse transcription coupled to the polymerase chain reaction showed a greatly diminished level of GRF receptor mRNA in the pituitaries of lit~lit mice as compared with lit~ + controls. Low level of message could re-flec~\a primary molecular defect or be due to secondary hypoplasia of somatotropes. These genetic and molecular data suggest that the Ghrfr gene is mutated in the lit mouse.