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

David C. Kohrman; Nicholas W. Plummer; Timothy Schuster; Julie M. Jones; Wonhee Jang; Daniel L. Burgess; James Galt; Brett T. Spear; Miriam H. Meisler

doi:10.1016/0888-7543(95)80198-U

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

David C. Kohrman, Nicholas W. Plummer, Timothy Schuster, Julie M. Jones, Wonhee Jang, Daniel L. Burgess, James Galt, Brett T. Spear, Miriam H. Meisler

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

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 med^J/ + mice. The new allele is designated med^TgNA4Bs (med^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.

Original language	English
Pages (from-to)	171-177
Number of pages	7
Journal	Genomics
Volume	26
Issue number	2
DOIs	https://doi.org/10.1016/0888-7543(95)80198-U
State	Published - 1995

Bibliographical note

Funding 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.

ASJC Scopus subject areas

Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/0888-7543(95)80198-U

Cite this

@article{64ff0b1371e840de90674db7e901a086,

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.",

author = "Kohrman, {David C.} and Plummer, {Nicholas W.} and Timothy Schuster and Jones, {Julie M.} and Wonhee Jang and Burgess, {Daniel L.} and James Galt and Spear, {Brett T.} and Meisler, {Miriam H.}",

note = "Funding 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.",

year = "1995",

doi = "10.1016/0888-7543(95)80198-U",

language = "English",

volume = "26",

pages = "171--177",

number = "2",

}

TY - JOUR

T1 - Insertional mutation of the motor endplate disease (med) locus on mouse chromosome 15

AU - Kohrman, David C.

AU - Plummer, Nicholas W.

AU - Schuster, Timothy

AU - Jones, Julie M.

AU - Jang, Wonhee

AU - Burgess, Daniel L.

AU - Galt, James

AU - Spear, Brett T.

AU - Meisler, Miriam H.

N1 - Funding 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.

PY - 1995

Y1 - 1995

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0028922292&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028922292&partnerID=8YFLogxK

U2 - 10.1016/0888-7543(95)80198-U

DO - 10.1016/0888-7543(95)80198-U

M3 - Article

C2 - 7601440

AN - SCOPUS:0028922292

SN - 0888-7543

VL - 26

SP - 171

EP - 177

JO - Genomics

JF - Genomics

IS - 2

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this