title: Insertional mutation of the motor endplate disease (med) locus on mouse chromosome 15.
abstract: 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.
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor 48109-0618, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Kohrman
authors.forename: N W
authors.initials: NW
authors.lastname: Plummer
authors.forename: T
authors.initials: T
authors.lastname: Schuster
authors.forename: J M
authors.initials: JM
authors.lastname: Jones
authors.forename: W
authors.initials: W
authors.lastname: Jang
authors.forename: D L
authors.initials: DL
authors.lastname: Burgess
authors.forename: J
authors.initials: J
authors.lastname: Galt
authors.forename: B T
authors.initials: BT
authors.lastname: Spear
authors.forename: M H
authors.initials: MH
authors.lastname: Meisler
mesh_terms: D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D002874:Chromosome Mapping; D058967:Contactin 1; D058966:Contactins; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009045:Motor Endplate / Q000473:pathology*; D016254:Mutagenesis, Insertional; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009468:Neuromuscular Diseases / Q000235:genetics*; D011689:Purkinje Cells / Q000473:pathology; D017384:Sequence Deletion; D050863:Synaptotagmin I; D050857:Synaptotagmins
chemical_list: C548669:CNTN1 protein, human; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C548670:Cntn1 protein, mouse; D058967:Contactin 1; D058966:Contactins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D050863:Synaptotagmin I; C494311:Syt1 protein, mouse; D050857:Synaptotagmins