Genetic Mapping and Analysis of Somatostatin Expression in Snell Dwarf Mice

Mice homozygous for the gene dwarf (dw) have elevated levels of somatostatin (SS) in extra-hypothalamic brain regions. By in situ hybridization, increased levels of SS mRNA were observed in regions shown previously to contain higher levels of the SS peptide. Thus, the rate of transcription and/or the stability of SS mRNA are affected by the dw mutation. Since both dw and the gene encoding SS, Smst, are located on mouse chromosome 16, two backcrosses segregating dw and Smst were used to determine whether dw is an allele of Smst. In one backcross, an inbred strain derived from the subspecies Mus musculus molossinus was used to provide a high degree of DNA sequence polymorphism. The gene order and map distances determined on this backcross were: (centromere) - Prm-1 - 7 - Igl-1 - 3 - Smst - 29 - dw - 15 - Sod-1 - 4 - Ets-2, demonstrating clearly that Smst and dw are distinct genes. Additional evidence against a primary role for SS excess in the pathogenesis of dw/dw mice was obtained by injecting normal newborn mice with a potent SS analog (cyclo II). In contrast to the pattern of cell loss observed in the dwarf anterior pituitary, the pituitaries of injected mice were indistinguishable from normal controls, further suggesting that the Smst locus is not the primary site of dw gene action.