This study focuses on the genetics of mutant mouse, shiverer, which has a grossly deficient amount of myelin in the central nervous system and a normal amount in the peripheral nervous system. In both sites, homozygous affected animals lack a particular myelin protein constituent named myelin basic protein (MBP). A second mutant allele, named myelin deficient, has a less severe impairment of myelin formation.
The first aim of the present study is to extend our preliminary results om mapping of the shiverer genetic locus to chromosome 18 by further matings with fused phalanges (near the middle of the chromosome) and twirler (closer to the centromere). We will also continue our initial matings (now at N2 and N3) that aim toward deveopment of congenic lines of shiverer and of myelin deficient with C57BL/6J, BALB/cBy, DBA/2J, and C3H/HeJ mice. The first use of these lines, even before congenic status is achieved, will be to test for linkage between shiverer and Peptidase-1, and the second use, when the lines are relatively stable, will be to compare shiverer and myelin deficient on the same genetic background. These congenic lines will form the essential baseline for most future studies on myelination with this mutant. Further, we plan to use availble monoclonal antibodies to MBP as probes to seek structural variants of MBP among mouse inbred strains and subspecies, and thereby to identify and map structural genes for MBP, as well as to determine if one of them is the same as shiverer. Finally, we will seek genes that regulate the development and amount of MBP, based on quantitative differences among strains. These mouse studies will complement analyses by other methods of molecular genetics, and are basic to an understanding of myelin structure, function and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021872-03
Application #
3403553
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1983-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1987-03-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
Rho, J H; Sidman, R L (1986) Intracellular injection of lucifer yellow into lightly fixed cerebellar neurons. Neurosci Lett 72:21-4
Shen, X Y; Billings-Gagliardi, S; Sidman, R L et al. (1985) Myelin deficient (shimld) mutant allele: morphological comparison with shiverer (shi) allele on a B6C3 mouse stock. Brain Res 360:235-47