Factors Contributing to the Poor Myelination in the Brain of the Snell Dwarf Mouse

Abstract

Conventional histological examination of the pituitary does not ditinguish Snell dwarf mutants (dw/dw) from their normal littermates (+/?) in the neonatal stage. Immunohistochemical examination of pituitaries of litters born to heterozygous Snell parents revealed that in .apprx. 25% of the glands examined, the number of positive cells was very low in the neonatal stage. The delineation of the events resulting in the poor myelination in the brain of the Snell dwarf mouse was attempted. An immunohistochemical method for identifying the mutant neonate was devised. Differences in the brain weights of the dw/dw and +/? mice first became apparent on the 10th day of age, and from this time on no further increase in the weight of the dwarf mouse brain was recorded. Increase in CNPase [2'',3''-cyclic nucleotide 3''-phosphohydrolase] activity was suppressed in the cerebrum and brain stem throughout the developmental stage, but not in the other parts of the brain. The yield of isolated myelin decreased by 58% in the mutant mouse, but CNPase activity was equivalent to that of control myelin. Differences in DNA content per cerebrum from the dw/dw and +/? mice first became apparent on the 10th day of age. The dw/dw mice showed no further increase, although the +/? mice continued to increase. [3H]thymidine incorporation into the DNA fraction in vivo on the 7th day of age, when glial cell proliferation in the cerebrum is most active, was suppressed to .apprx. 50% of the control level in all parts of the dwarf brain. Poor myelination found in the mutant cerebrum is probably a hypomyelination due to reduced olgiodendroglial proliferation caused by lack of circulating growth hormone.