Comparison of Trembler and Trembler-J mouse phenotypes: varying severity of peripheral hypomyelination

Abstract

Trembler (Tr) is an autosomal dominant mutation which produces hypomyelination and demyelination in the mouse peripheral nervous system. This paper compares the genetic, behavioral, and pathological aspects of trembler-J, (TrJ) to those of the original Tr mutation. We found that TrJ was tightly linked on chromosome 11 to vestigial tail, vt, as is Tr. Most TrJ/? animals were more mildly affected behaviorally and pathologically than Tr/? animals. Tr/? animals were rather uniformly affected. In contrast, with matings of mildly affected TrJ/? (putative TrJ/+) animals to each other, and not with matings of putative TrJ/+ X +/+, some offspring, putative homozygotes, TrJ/TrJ, were more severely affected behaviorally and had more extreme peripheral hypomyelination than any Tr/? animals. In spite of their differences, Tr/?, putative TrJ/+, and putative TrJ/TrJ animals shared a failure or marked delay of Schwann cells to progress from the stage of axonal ensheathment in a 1:1 relationship to myelination. We conclude that Tr and TrJ are probably allelic, and that despite their phenotypic differences, their actions are fundamentally similar. While Tr is a dominant, we believe that TrJ behaves as a semidominant, which in homozygotes, TrJ/TrJ, produces the most severe heritable peripheral myelin deficiency hitherto described.