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 medJ/ + mice. The new allele is designated medTgNA4Bs (medtg). 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.
|Number of pages||7|
|State||Published - 1995|
Bibliographical noteFunding Information:
We are grateful to Lucy Rowe for analyzing the data from The Jackson Laboratory backcross. We thank Dr. Barbara Rantsch for providing the contactin 1 cDNA clone and Dr. Thomas Sudhof for the synaptotagmin 1 cDNA. We are grateful to Dr. Sally Camper for providing TaqI blots from the BSS backcross and to Dr. Karin Wiebauer for assistance with construction of the cosmid library. This work was supported by USPHS Grants GM24872 (M.H.M.) and GM45253 (B.T.S.) and Council for Tobacco Research Grant 3512 (B.T.S.). We thank Michael Green (U. of Kentucky Transgenic Animal Facility) for production of the transgenic mice. David Kohrman is the recipient of National Research Service Award DC00109. Nicholas Plummer was supported by the University of Michigan Training Program in Genetics (R32 GM07544). Dan Burgess acknowledges support from the Developmental Biology Training Program (R32 HD07274). Wonhee Jang is recipient of a Barbour Fellowship from the Rackham Graduate School of the University of Michigan.
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