International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 98 - IDENTIFICATION OF A MISSENSE MUTATION RESPONSIBLE FOR NEUROMUSCULAR DEGENERATION IN mnd2 MICE

Jones JM
Department of Human Genetics

Co-Authors: 1) Ji W, 2) Saunders T L, 2) Van Keuren M L, 1) Meisler M H
Institutions: 1) Department of Human Genetics, 2) Transgenic Model Laboratory, University of Michigan

mnd2 is a spontaneous autosomal recessive disorder characterized by neuromuscular degeneration. The mutation was discovered in a colony of C57BL/6J mice at the University of Michigan in 1990. Affected mice can be identified at P25 by failure to grow and mild ataxia. The disease progresses with development of repetitive movements, chorea and dystonia. In the final stages, there is akinesis leading to death between P30 and P40. The mnd2 gene was mapped to a 950 kb region of mouse chromosome 6 in a B6XCASTcross and further localized to 250 kb in a B6XSJL cross. Transgene rescue by overlapping BAC clones and one BAC carrying a deletion narrowed the target region to a 40 kb interval containing 6 candidate genes. Genomic sequencing of the region identified an A to T nucleotide substitution that changes an evolutionarily conserved serine residue to cysteine in a gene with enzymatic activity. The missense mutation results in reduced activity in mnd2 tissues and in cells transfected with the mutant cDNA. Function is restored in BAC- rescued animals. Further characterization of the mnd2 gene will be presented.


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