These mice carry a spontaneous neurological mutation (nm3419) in the Uchl1 gene that results in progressive motor defects, weight loss and early homozygous lethality by approximately 200 days of age.
Gregory Cox, The Jackson Laboratory
Scott Wilson, University of Alabama, Birmingham
The ubiquitin proteasome system has been shown to regulate numerous cellular functions by controlling protein degradation. Both increases and decreases in protein turnover have been implicated in several genetic forms of neurodegeneration.
These mice carry a spontaneous neurological mutation in the Uchl1 (ubiquitin carboxy-terminal hydrolase L1) gene, which expresses one of the most abundant proteins in neurons. A 795 bp deletion involving exon 6 and intron 6 results in a complete loss of protein expression. Homozygotes are born in Mendelian fashion and first display motor incoordination at 4 weeks of age, as measured by elevated beam analysis. Motor defects increase in severity over the next 4 weeks and, by 16 weeks of age, the mice are unable to successfully cross the elevated beam. By approximately 20 weeks of age, there is a significant decrease in viability, and most of the homozygous mice die by 28 weeks of age. Their decline is correlated with a significant decrease in body mass.
A spontaneous 795 bp deletion, encompassing the final 24 bp of exon 6 and the first 771 bp of intron 6, occurred in the BALB/cJ colony at The Jackson Laboratory. As a result of the mutation, 99 bp of intron 6 are included in the resulting mRNA and a cryptic splice donor within intron 6 is used to splice the mRNA to exon 7. The included intron 6 sequence encodes 13 novel amino acids before a premature termination codon is encountered. This results in the complete loss of protein expression. This strain was backcrossed to C57BL/6J for 7 generations.
|Allele Name||gracile axonal dystrophy Jackson|
|Allele Synonym(s)||Uchl1nm3419; Uch-L1nm3419|
|Gene Symbol and Name||Uchl1, ubiquitin carboxy-terminal hydrolase L1|
|Strain of Origin||BALB/cJ|
|Molecular Note||A 795 base-pair intragenic deletion resulted in the removal of the final 24 base-pairs of exon 6 and the first 771 base-pairs of intron 6. As a result of the mutation, 99 base-pairs of intron 6 are included in the mRNA and a cryptic splice donor within intron 6 is used to splice the mRNA to exon 7. The included intron 6 sequence encoded 13 novel amino acids before a premature termination codon was encountered, resulting in the loss of the final 78 amino acids of the protein. Immunoblot analysis of brain extracts failed to detect any protein.|
Heterozygotes are viable and fertile. Homozygotes develop motor coordination defects starting at 4 weeks of age and die by approximately 20 weeks of age.
When using the B6.C-Uchl1gad-J/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #024355 in your Materials and Methods section.