Heterozygote effects in dreher mice

The dreher mutation (gene symbol: dr) is an autosomal recessive mutation located on chromosome 1 of the mouse. Homozygous dreher mice (dr/dr) are ataxic, have a white belly spot, a short-tail, inner ear and skeletal malformations, and a variety of CNS abnormalities. Recently in our dreher colony (the drsst-J allele on a B6C3Fe background), we noticed mice with one or more white belly spots typical of drsst-J/drsst-J mice but which were non-ataxic and had a normal tail length; wild-type mice (+/+) of the same genetic background do not have simialr belly spots. Results of three breeding experiments indicate that a new mutation had not occurred, but rather that the spotted, non-ataxic mice are heterozygous dreher mice (drsst-J/+). Histological examination showed that drsst-J/+ mice have abnormalities in the hippocampal formation that are qualitatively similar to those found in drsst-J/drsst-J mice. Most frequently there is an increase in the number of pyramidal cells in CA3 and a marked thickening of the pyramidal cell layer. In contrast to dreher homozygotes the cerebellum appears to have a normal foliation pattern and no discernible laminar abnormalities. Thus, both breeding experiments and histological examination indicate that drsst-J is semidominant. We speculate that drsst-J is a "loss of function" mutation, but, in any event, the presence of phenotypic abnormalities in drsst-J/+ mice may be useful in identifying the primary developmental defect in dreher mice.