Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names C57BL/6J-Aspanur7/J    (Changed: 13-NOV-09 ) Type Chemically Induced Mutation; Mutant Stock; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Brian Popko,   University of Chicago

Description
Mice homozygous for this ENU-induced mutation, the neurological 7 (nur7) allele of Aspa (Aspa^nur7), are viable and fertile, although the donating investigator reports homozygotes are poor breeders. The Aspa^nur7 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 Aspa^nur7 mutant mice may be useful in studying the axonal pathology caused by central nervous system myelin defects.

Development
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 Aspa^nur7 mice (also harboring the In(11Trp53;11Wnt3)8Brd balancer) were bred together (C57BL/6J genetic background) for many generations. Homozygous Aspa^nur7 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.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Canavan Disease

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Aspa^nur7/Aspa^nur7

        involves: C57BL/6J

• nervous system phenotype
• abnormal myelination
  • at P21, myelin sheath thickness is reduced compared to in wild-type mice   (MGI Ref ID J:143201)
  • at P21, mice exhibit a 40% decrease in phosphatidyl ethanolamine in myelin compared to in wild-type mice   (MGI Ref ID J:143201)
  • at P21, normal fatty acid-containing Galc cerebroside is reduced 40% compared to in wild-type mice   (MGI Ref ID J:143201)
  • however, the level of hydroxyl fatty acid-containing Galc cerebroside is normal   (MGI Ref ID J:143201)
  • myelin degeneration is more pronounced at P70 than at P21   (MGI Ref ID J:143201)
• abnormal oligodendrocyte morphology
  • at P21, loss of oligodendrocytes occurs in lesion areas unlike in wild-type mice   (MGI Ref ID J:143201)
  • at P30, oligodendrocyte loss occurs in the spinal cord gray matter unlike in wild-type mice   (MGI Ref ID J:143201)
  • at P70, the number of oligodendrocytes is increased in the brainstem (medial pons) and spinal cord gray matter   (MGI Ref ID J:143201)
• astrocytosis   (MGI Ref ID J:143201)
• axon degeneration
  • at P120, 30% fewer axons are found in the cerebellar white matter compared to in heterozygous mice   (MGI Ref ID J:143201)
• brain vacuoles
  • at P14, vacuoles are detected in the cerebellar white matter in the Purkinje cell layer and brainstem unlike in wild-type mice   (MGI Ref ID J:143201)
  • mice exhibit progressive vacuolar degeneration that affects the forebrain, cerebral cortex, hippocampus, subcortical white matter regions, midbrain, pons and cerebellum where the granule cell layer, Purkinje cell layer and white matter show defects unlike in wild-type mice   (MGI Ref ID J:143201)
  • lateral sections of the cerebellar sagittal plane exhibit more increasingly severe white matter lesions   (MGI Ref ID J:143201)
  • at P70, vacuolization expands into subcortical white matter, brainstem, cerebellum and spinal cord gray matter   (MGI Ref ID J:143201)
  • at P70, the dorsal pons is more severely affected than the rest of the pons by vacuolization   (MGI Ref ID J:143201)
  • vacuolization is caused by the splitting of the myelin sheath   (MGI Ref ID J:143201)
• enlarged lateral ventricles
  • widened at P70   (MGI Ref ID J:143201)
• seizures
  • as mice age   (MGI Ref ID J:143201)
• spongiform encephalopathy
  • beginning at P14, mice exhibit progressive spongiform degeneration   (MGI Ref ID J:143201)
  • mice exhibit progressive neuropathy similar to in Aspa^nur7/Aspa^nur7 Ugt8a^tm1Pop/Ugt8a⁺ mice   (MGI Ref ID J:143201)
• behavior/neurological phenotype
• abnormal gait
  • at P21, mice exhibit a wide ataxic gait   (MGI Ref ID J:143201)
• ataxia
  • at P21, mice exhibit a wide ataxic gait   (MGI Ref ID J:143201)
  • at P70, ataxia is slightly increased compared to in younger mice   (MGI Ref ID J:143201)
• hypoactivity
  • animals have reduced open field activity   (MGI Ref ID J:85113)
  • young mice are hypoactive   (MGI Ref ID J:143201)
• impaired coordination
  • at P42 to P56, mice exhibit a 50% decreased in latency to fall on a rotarod compared to wild-type mice   (MGI Ref ID J:143201)
• lethargy   (MGI Ref ID J:85113)
• seizures
  • as mice age   (MGI Ref ID J:143201)
• tremors
  • late onset; develop upon movement   (MGI Ref ID J:85113)
  • adult mice tremble during movement   (MGI Ref ID J:143201)
  • mice develop more severe tremors as they age   (MGI Ref ID J:143201)
  • at P70, tremors are slightly increased compared to in younger mice   (MGI Ref ID J:143201)
• growth/size phenotype
• decreased body size   (MGI Ref ID J:143201)
  • affected animals are smaller than littermates   (MGI Ref ID J:85113)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Neurobiology Research
Ataxia (Movement) Defects
Epilepsy
Myelination Defects
Neurodegeneration
Neuromuscular Defects
Tremor Defects

Research Tools
Genetics Research
      Mutagenesis and Transgenesis
      Mutagenesis and Transgenesis: Production of Chemical Mutations
Neurobiology Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Aspanur7
Allele Name		neurological 7
Allele Type		Chemically induced (ENU)
Common Name(s)		neurological (nur) 07; nurm07Jus; small lethargic;
Strain of Origin		C57BL/6J
Gene Symbol and Name		Aspa, aspartoacylase
Chromosome		11
Gene Common Name(s)		ACY2; ASP; Acy-2; Acy2; aminoacylase 2; neurological 7; nur7; small lethargic;
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. [MGI Ref ID J:143201]

Genotyping

Genotyping Information

Genotyping Protocols

8607 Aspa, Pyrosequencing

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kile BT; Hentges KE; Clark AT; Nakamura H; Salinger AP; Liu B; Box N; Stockton DW; Johnson RL; Behringer RR; Bradley A; Justice MJ. 2003. Functional genetic analysis of mouse chromosome 11. Nature 425(6953):81-6. [PubMed: 12955145]  [MGI Ref ID J:85113]

Traka M; Wollmann RL; Cerda SR; Dugas J; Barres BA; Popko B. 2008. Nur7 is a nonsense mutation in the mouse aspartoacylase gene that causes spongy degeneration of the CNS. J Neurosci 28(45):11537-49. [PubMed: 18987190]  [MGI Ref ID J:143201]

Additional References

Aspa^nur7 related

Boles MK; Wilkinson BM; Wilming LG; Liu B; Probst FJ; Harrow J; Grafham D; Hentges KE; Woodward LP; Maxwell A; Mitchell K; Risley MD; Johnson R; Hirschi K; Lupski JR; Funato Y; Miki H; Marin-Garcia P; Matthews L; Coffey AJ; Parker A; Hubbard TJ; Rogers J;Bradley A; Adams DJ; Justice MJ. 2009. Discovery of candidate disease genes in ENU-induced mouse mutants by large-scale sequencing, including a splice-site mutation in nucleoredoxin PLoS Genet 5(12):e1000759. [PubMed: 20011118]  [MGI Ref ID J:161341]

Lang J; Maeda Y; Bannerman P; Xu J; Horiuchi M; Pleasure D; Guo F. 2013. Adenomatous polyposis coli regulates oligodendroglial development. J Neurosci 33(7):3113-30. [PubMed: 23407966]  [MGI Ref ID J:194259]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygous mice may be bred. The donating investigator reports that homozygous mice are poor breeders.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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