B6(CBy)-Usp14^nmf375/SwiJ

Stock number: 036400
Product name: nmf375
Research areas: Developmental Biology Research, Neurobiology Research

Detailed description

Usp14 (ubiquitin specific peptidase 14) encodes a member of the ubiquitin-specific processing (UBP) family of proteases that functions as a deubiquitinating enzyme. nmf375 is a recessive ENU-induced mutation in Usp14; the mutation is a C to T point mutation in intron 9 that results in a 95% reduction of USP14 protein expression. On the C57BL/6 background (this strain), homozygous nmf375 mutants die embryonically or within hours after birth. However, on the BALB/c background nmf375 homozygotes live past 8 months of age, but exhibit a progressive deterioration of motor performance, depletion of monomeric ubiquitin and motor endplate disease and die by 50 weeks of age.

Of note, the mixed background strain is distributed as B6;CByJ-Usp14^nmf375/J (Stock No. 005750).

Development

nmf375 is a T to C point mutation in position 4 of the splice site donor region of intron 9 of the Usp14 gene on chromosome 18.  The mutation was generated by ethylnitrosourea (ENU) mutagenesis in C57BL/6J males in the Neuroscience Mutagenesis Facility (NMF) at The Jackson Laboratory. Mutagenized males were outcrossed to C57BL/6J females. The mutation results in aberrant mRNA splicing and a 95% reduction in USP14 protein. nmf375 was then outcrossed to BALB/cByJ mice and maintained as B6;CByJ-Usp14^nmf375/J (Stock No. 005750). Dr. Scott Wilson (University of Alabama at Birmingham) obtained the nmf375 mice and introgressed the allele into C57BL/6J for 10 generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.d

Allele

Symbol: Usp14^nmf375
Name: neuroscience mutagenesis facility, 375
MGI accession ID: MGI:3622127
Generation method: Chemically induced (ENU)
Attributes: Hypomorph
Synonyms: NMF375
Marker symbol: Usp14
Marker name: ubiquitin specific peptidase 14
Marker synonyms: 2610005K12Rik; 2610037B11Rik; ataxia; ax; dUB-type TGT; nmf375; TGT; Ubp6
Chromosome: 18
Strain of origin: C57BL/6J
Molecular note: ENU mutagenesis induced a T to C transition in position 4 of the splice site donor region of intron 9. Western blot anlaysis confirmed the absence of protein expression in the spinal cord without the detection of truncated proteins. Authors state that this allele is hypomorphic based on phenotypic analysis.