title: Exploring the mammalian neuromuscular system by analysis of mutations: spinal muscular atrophy and myotonia.
abstract: Any biological structure can be studied using mutations that interfere either with its emergence or its function. We investigate spontaneous and induced mutations in the mouse that affect neuromuscular development and function. The wobbler mouse (phenotype WR, genotype wr/wr) suffers from muscular atrophy because of the degeneration of 20-40% of the motoneurones; it is also unable to produce functional spermatozoa. As a step towards positional cloning of the wr gene, we have mapped the locus to proximal chromosome 11, thus excluding CNTF and its receptor as candidates, and suggesting the closely-linked Rab 1 gene encoding a GTP-binding protein as a possibility. In the case of the adr (arrested development of righting response) mouse, which shows hyperexcitability of mature muscle fibres due to a reduction of the 'dampening' function of chloride conductance at resting potential, we have shown that the defect is in the chloride channel gene adr/Clc-1 on chromosome 6. This allowed us to predict via synteny the chromosomal location of human Thomsen's and Becker's myotonias as close to the TCRB gene on human chromosome 7q. The combination of these approaches with gene-targeting approaches will allow genetic analysis of the establishment and structure of the neuromuscular system.
authors.affiliation: Developmental Biology Unit, University of Bielefeld, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Jockusch
authors.forename: K
authors.initials: K
authors.lastname: Kaupmann
authors.forename: M
authors.initials: M
authors.lastname: Gronemeier
authors.forename: M
authors.initials: M
authors.lastname: Schleef
authors.forename: R
authors.initials: R
authors.lastname: Klocke
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants; D009132:Muscles / Q000503:physiopathology*; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D009222:Myotonia / Q000235:genetics* / Q000503:physiopathology; D009420:Nervous System / Q000503:physiopathology*