HINDSHAKER, A NOVEL MYELIN MUTANT SHOWING HYPOMYELINATION PREFERENTIALLY AFFECTING THE SPINAL-CORD

Animals with spontaneous mutations affecting myelin formation have pro vided useful information about the genetic and cellular mechanisms reg ulating normal and abnormal myelination. In this paper we describe a n ovel murine mutation termed hindshaker (hsh), which is inherited in an autosomal recessive manner. Affected mice are characterised by a vari able tremor of the hind end which commences at about 2 weeks of age an d largely disappears in animals older than 6 weeks. There is hypomyeli nation affecting predominantly the spinal cord, although the optic ner ves and brain are involved to a much lesser degree. The defect of thin ly myelinated and naked axons is maximal at 20 days of age and largely resolves with time so that in the adult most axons are myelinated. Th e myelin structure appears normal and immunostains for the major prote ins. Although the distribution of oligodendrocytes in the spinal cord is similar to normal during the period of hypomyelination, there are f ewer mature cells. The hsh mutation appears to delay the maturation of oligodendrocytes, particularly in the spinal cord. Additionally, ther e is a considerable variation in phenotypic expression and in penetran ce when the mutation is expressed on different genetic backgrounds, su ggesting the hsh locus is subject to the influence of modifying gene(s ). Identification of the hsh gene should identify a factor important i n the development of oligodendrocytes, particularly those in the spina l cord.