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Originally published as Genetics Published Articles Ahead of Print on September 14, 2008.
Genetics, Vol. 180, 1419-1427, November 2008, Copyright © 2008
doi:10.1534/genetics.108.094227
A Targeted Deleterious Allele of the Splicing Factor SCNM1 in the Mouse
Viive M. Howell*,
Georgius de Haan*,1,
Sarah Bergren*,
Julie M. Jones*,
Cymbeline T. Culiat
,
Edward J. Michaud,
Wayne N. Frankel
and
Miriam H. Meisler*,2
* Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109-5618, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-6445 and The Jackson Laboratory, Bar Harbor, Maine 04609
2 Corresponding author: Department of Human Genetics, 4909 Buhl, University of Michigan Medical School, Ann Arbor, MI 48109-5618.
E-mail: meislerm{at}umich.edu
The auxiliary spliceosomal protein SCNM1 contributes to recognition of nonconsensus splice donor sites. SCNM1 was first identified as a modifier of the severity of a sodium channelopathy in the mouse. The most severely affected strain, C57BL/6J, carries the variant allele SCNM1R187X, which is defective in splicing the mutated donor site in the Scn8amedJ transcript. To further probe the in vivo function of SCNM1, we constructed a floxed allele and generated a mouse with constitutive deletion of exons 3–5. The SCNM1
3-5 protein is produced and correctly localized to the nucleus, but is more functionally impaired than the C57BL/6J allele. Deficiency of SCNM1 did not significantly alter other brain transcripts. We characterized an ENU-induced allele of Scnm1 and evaluated the ability of wild-type SCNM1 to rescue lethal mutations of I-mfa and Brunol4. The phenotypes of the Scnm13-5 mutant confirm the role of this splice factor in processing the Scn8amedJ transcript and provide a new allele of greater severity for future studies.
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