Heterozygote Effects in Dreher Mice

Abstract

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 dr^sst-J allele on a B6C3Fe background), we noticed mice with one or more white belly spots tyical of dr^sst-J /dr^sst-Jmice 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 (dr^sst-J /+). Histological examination showed that dr^sst-J/+ mice have abnormalities in the hippocampal formation that are qualitatively similar to those found in dr^sst-J /dr^sst-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 df^sst-J is semidominant. We speculate that dr^sst-J is a “loss of function” mutation, but, in any event, the presence of phenotypic abnormalities in dr^sst-J/+ mice may be useful in identifying the primary developmental defect in dreher mice.

Key Words:

• hippocampus
• pyramidal cells
• cerebellum
• ectopic neurons