Structural analysis of rodent growth hormone genes: application to genetic forms of hypopituitarism

Analysis of GH gene structure in the mouse permits evolutionary comparisons with GH gene structure in the rat and provides information about the mechanism responsible for heritable deficiencies of anterior pituitary hormones. The little mutation in mice is analogous to autosomal recessive, isolated, partial deficiency of GH in man, whereas the Snell dwarf mutation is a model for autosomal recessive deficiency of GH, TSH, and PRL. Mouse cellular DNA was digested with the restriction enzymes Eco RI, Bam HI, Bgl II, Hind III, and Kpn I, singly and in combination. Gene sequences containing coding information for GH were detected by hybridization to a radiolabeled recombinant DNA probe complementary to a rat GH mRNA. The results of genomic restriction analysis indicate that there is a single type of mouse GH gene sequence per haploid genome with a length equal to or less than 32000 base pairs. The distances separating 6-base restriction sites close to the mouse GH gene differ from those close to the rat GH gene. A Kpn I site in the codons for amino acids 103 and 104 of rat GH is absent in the mouse gene. Restriction patterns of DNA from little and Snell dwarf mice did not differ from those of normal mice, indicating that these mutations do not involve deletions of the mouse GH gene.