The ENU-induced neurological 7 (nur7) allele of aspartoacylase (Aspanur7) results from a Q193X transition generating a nonsense codon and a loss-of-function mutation. Homozygous Aspanur7 mice display a Canavan disease-related pathology and may be useful in studying the axonal pathology caused by central nervous system myelin defects.
Brian Popko, University of Chicago
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Chemically induced (ENU) | Aspa | aspartoacylase |
Mice homozygous for this ENU-induced mutation, the neurological 7 (nur7) allele of Aspa (Aspanur7), are viable and fertile, although the donating investigator reports homozygotes are poor breeders. The Aspanur7 mutation encodes a Q193X transition that generates a nonsense codon and results in a predicted 120 amino acid truncation of the protein. While mutant Aspa mRNA expression is reduced by 40% (compared to wildtype), no truncated Aspa protein expression is reported in homozygous oligodendrocytes or brain tissue. Homozygous mice display early-onset spongy degeneration of central nervous system myelin with increased NAA levels similar to that observed in Canavan disease; an Aspa-deficiency-induced fatal childhood autosomal recessive leukodystrophy. Homozygous mice are easily distinguished at 21 days of age by their small body size and a wide-based ataxic gait. Neurological disease progresses with age to tremors and seizures. These Aspanur7 mutant mice may be useful in studying the axonal pathology caused by central nervous system myelin defects.
These mutant mice were created by the laboratory of Dr. Monica Justice (Baylor College of Medicine) using multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder C57BL/6J mice. Genetic screening was utilized to identify mice with a neurological phenotype described as hypoactive in young postnatal mice and trembling during movement in adulthood ("small, lethargic, tremors in adults"). Using a candidate gene approach, a region of chromosome 11 containing the aspartoacylase (Aspa) gene was associated with the mutant phenotype. Sequencing of this gene identified a C->T transition in nucleotide 577 in exon 4 (coding a Q193X mutation that generates a TAA stop/nonsense codon and results in the early termination of the protein). Heterozygous Aspanur7 mice (also harboring the In(11Trp53;11Wnt3)8Brd balancer) were bred together (C57BL/6J genetic background) for many generations. Homozygous Aspanur7 mice (not harboring the In(11Trp53;11Wnt3)8Brd balancer) were sent to The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
A 27 SNP (single nucleotide polymorphism) panel analysis performed by The Jackson Laboratory revealed 7 of 27 markers that were not C57BL/6 allele-type. These data suggest 129, C3H, or CBA (and perhaps other) genetic contamination prior to arrival at The Jackson Laboratory.
Allele Name | neurological 7 |
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Allele Type | Chemically induced (ENU) |
Allele Synonym(s) | neurological (nur) 07; nurm07Jus; small lethargic |
Gene Symbol and Name | Aspa, aspartoacylase |
Gene Synonym(s) | |
Strain of Origin | C57BL/6J |
Chromosome | 11 |
Molecular Note | Exon 4 contains a point mutation of C to T at position 577 that results in an amino acid substitution of a stop codon for glutamine at position 193 (Q193X). The absence of protein expression was confirmed by western blot on brain extracts. |
When maintaining a live colony, heterozygous mice may be bred. The donating investigator reports that homozygous mice are poor breeders.
When using the STOCK Aspanur7/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008607 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Aspa<nur7> |
Frozen Mouse Embryo | STOCK Aspa<nur7>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Aspa<nur7>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Aspa<nur7>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | STOCK Aspa<nur7>/J Frozen Embryo | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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