Insertional mutation of the motor endplate disease (med) locus on mouse chromosome 15

Journal Article · Mon Mar 20 04:00:00 EST 1995 · Genomics

DOI:https://doi.org/10.1016/0888-7543(95)80198-U· OSTI ID:219877

Kohrman, D C; Plummer, N W; Schuster, T ^[1]

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1. Univ. of Michigan, Ann Arbor, MI (United States); and others

Homozygous transgenic mice from line A4 have an early-onset progressive neuromuscular disorder characterized by paralysis of the rear limbs, muscle atrophy, and lethality by 4 weeks of age. The transgene insertion site was mapped to distal chromosome 15 close to the locus motor endplate disease (med). The sequence of mouse DNA flanking the insertion site junctions was determined. A small (<20 kb) deletion was detected at the insertion site, with no evidence of additional rearrangement of the chromosomal DNA. Noncomplementation of the transgene-induced mutation and med was demonstrated in a cross with med{sup J}/ + mice. The new allele is designated med{sup TgNA4Bs}(med{sup tg}). The homologous human locus MED was assigned to chromosome 12. Synaptotagmin 1 and contactin 1 were eliminated as candidate genes for the med mutation. The transgene-induced allele provides molecular access to the med gene, whose function is required for synaptic transmission at the neuromuscular junction and long-term survival of cerebellar Purkinje cells. 49 refs., 5 figs., 1 tab.

• OSTI ID: 219877
• Journal Information: Genomics, Journal Name: Genomics Journal Issue: 2 Vol. 26; ISSN 0888-7543; ISSN GNMCEP
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CHROMOSOMAL ABERRATIONS
CHROMOSOMES
DNA SEQUENCING
GENE MUTATIONS
GENES
GENETIC MAPPING
HUMAN CHROMOSOME 12
MUSCLES
NERVOUS SYSTEM DISEASES
POLYMERASE CHAIN REACTION
TRANSGENIC MICE