Mapping of taiep rat phenotype to rat Chromosome 9.
The taiep mutant rat was first described in a colony of Sprague-Dawley rats at the University of Puebla in 1989, with an autosomal recessive inherited pattern. taiep is an acronym for the progressive neurologic deficits that the rat develops, i.e., t = trembling (3-4 weeks), a = ataxia (at 4 months), i = immobility (5-6 months), e = epilepsy (5-6 months), andp = paresis (7 months onwards). Thus, mutant rats are first identified by a tremor at 3-4 weeks of age that is followed by a progressive neurological worsening (Holmgren et al. 1989; Lunn et al. 1997). The cause of the neurological symptoms is an early failure of normal myelination of the central nervous system (CNS) followed by progressive demyelination of certain CNS tracts (Lunn et al. 1997). We have been exploring the underlying pathophysiology of the mutant and have determined that the myelin defect results from the progressive accumulation of microtubules in oligodendrocytes, the myelin-producing cells of the CNS (Song et al. 1999). Microtubules are the major component of the cytoskeleton of this and many other cells of the body, and microtubule-based transport of protein and mRNA is essential for normal cell function. There is no direct human counterpart of the taiep rat. Nonetheless, providing an understanding of the control of microtubule dynamics in the oligodendrocyte will be highly relevant to our knowledge of the cell biology of the myelinating cell of the CNS. This information is of great relevance to the function of the cell in human myelin disorders and in experimental remyelination. As the taiep rat apparently has a primary disorder in the oligodendrocyte cytoskeleton, it is an ideal model in which to study this process. This information may also be a key to the complete understanding of the mechanism of microtubule assembly/disassembly in many cell types.
Li
Fang-Yuan
FY
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison Madison, Wisconsin 53706, USA. lif@svm.vetmed.wisc.edu
Song
Jonathan
J
Duncan
Ian D
ID
D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D003599:Cytoskeleton / Q000378:metabolism; D019992:Databases as Topic; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D009422:Nervous System Diseases / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D011995:Recombination, Genetic
D012333:RNA, Messenger