Overview

This ENU-induced mutant mouse strain expresses an altered Rnu2-8 U2 snRNA gene. Homozygous mice exhibit a progressive ataxia and neurodegeneration. This mutant line may have applications in studies related to neuron degeneration and the regulation of U2 snRNA gene processing.

Donating Investigator

Sue Ackerman, The Jackson Laboratory

Genetic overview

Genetic Background	Generation

Rnu2-8^nmf291

Allele Type	Gene Symbol	Gene Name
Chemically induced (other)	Rnu2-8	U2 small nuclear RNA 8

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Research Applications

Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

U2 small nuclear RNA (Rnu2-8) is one of five small nuclear RNAs, which comprise the spliceosome machinery and are responsible for the splicing of pre-mRNAs. The ethylmethanesulfonate (EMS)-induced nmf291 allele is a 5 base pair deletion, which results in alternative splicing defects, including the retention of small introns. Mice homozygous for the mutation exhibit mild tremors beginning at 4 weeks of age and progress to truncal ataxia by 12 weeks of age. The ataxia is characterized by splayed hind feet, a lumbering gait and a tendency to intermittently jump into the air. Granule cell degeneration begins at 4 weeks of age and occurs mainly in the cerebellum, but later progresses to the dentate gyrus region of the hippocampus.

Mice heterozygous for the mutation develop late onset (2 years) tremors and some granule cell degeneration. Standard pathology work-up on three mutants (84 -138 days of age) revealed severe loss of granule cells.

Both female and male homozygotes breed, but the reproductive window is shortened by the progressive physical impairments, females may have difficulties taking care of litters. This strain may be useful for studying pre-mRNA splicing and neurodegeneration.

Development

This mutation was induced in (C57BL/6J x 129S4/SvJae)F1 derived v6.4 ES cells via exposure to ethylmethanesulfonate (EMS)during a forward genetic screen for recessive neurological phenotypes at the Neuroscience Mutagenesis Facility at The Jackson Laboratory. The mutation results in a 5 base pair deletion between nucleotides 30 and 34 in a highly conserved region of the Rnu2-8 transcription unit. The deletion removes the first 2 nucleotides of the U2 consensus branch site recognition sequence (BRSR) and a 3 nucleotide linker between BRSR the U2/U6 helix. This strain has been backcrossed to C57BL/6J for two generations and was cryopreserved in 2004.

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Jia Y; Mu JC; Ackerman SL. 2012. Mutation of a U2 snRNA gene causes global disruption of alternative splicing and neurodegeneration. Cell 148(1-2):296-308PubMed: 22265417 MGI: J:179357

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Genetics

Rnu2-8^nmf291

Allele Symbol: Rnu2-8^nmf291

Allele Name	neuroscience mutagenesis facility, 291
Allele Type	Chemically induced (other)
Allele Synonym(s)
Gene Symbol and Name	Rnu2-8, U2 small nuclear RNA 8
Gene Synonym(s)
Strain of Origin	(C57BL/6J x 129S4/SvJae)F1
Chromosome	11
Molecular Note	This phenotypic allele was identified in an ethylmethanesulfonate (EMS) mutagenesis screen for neurological phenotypes. The molecular defect is a 5 base pair deletion between nucleotides 30 and 34 in a highly conserved region located in the U2 consensus branch site sequence (BSRS) and the linker region between the BSRS and the U2/U6 helix.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Rnu2-8^nmf291 related

Neurobiology Research
- Ataxia (Movement) Defects
- Cerebellar Defects
- Neurodegeneration
- Neuroscience Mutagenesis Facility Strain

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Rnu2-8^nmf291/Rnu2-8^nmf291
B6;129-Rnu2-8/J

behavior/neurological phenotype

abnormal gait
- early manifestations of the mutant phenotype are a tendency to walk on the toes of the hind feet and a slight side-to-side sway; by approximately 11 weeks of age, mutant mice exhibit a staggering gait with a pronounced side-to-side sway that sometimes causes them to lose their balance and fall over
- ses them to lose their balance and fall over

muscle phenotype

progressive muscle weakness
- mutant mice exhibit progressive hind limb weakness, evidenced by splaying of their hind legs during locomotion

nervous system phenotype

abnormal cerebellum morphology
- standard pathology screen of three mutants aged 84-138 days revealed severe loss of granule cells

Genotype: Rnu2-8^nmf291/Rnu2-8^nmf291
involves: 129S4/SvJae * C57BL/6J

behavior/neurological phenotype

ataxia
- mice develop mild tremors by 8 weeks age and progress to truncal ataxia by 12 weeks of age

nervous system phenotype

abnormal cerebellar granule cell morphology
- granule cells with pyknotic nuclei are observed beginning at 4 weeks of age

decreased cerebellar granule cell number
- granule cells undergo apoptosis beginning at P30, by 4 months of age most granule cells have degenerated

neuron degeneration
- cerebellar granule cells undergo apoptosis beginning at P30, by 4 months of age most granule cells have degenerated
- granule cell degeneration in the dentate gyrus region of the hippocampus is observed in 4 month old mice

small cerebellum
- overall size of cerebellum is dramatically reduced in 4 month old mice

Genotype: Rnu2-8^nmf291/Rnu2-8⁺
involves: 129S4/SvJae * C57BL/6J

behavior/neurological phenotype

tremors
- mild tremors are observed in 2 year old mice

nervous system phenotype

decreased cerebellar granule cell number

neuron degeneration
- apoptotic cerebellar granule cells are first observed in 1 month old mice, however, neuron loss is considerably less than in homozygous mice

small cerebellum
- overall size of the cerebellum is reduced in 2 year old mice

References

Jia Y; Mu JC; Ackerman SL. 2012. Mutation of a U2 snRNA gene causes global disruption of alternative splicing and neurodegeneration. Cell 148(1-2):296-308PubMed: 22265417 MGI: J:179357

Additional - Rnu2-8^nmf291 related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:JR5048 sequencing assay
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homozygotes, however,the reproductive window is shortened by the progressive physical impairments.
- Additional Breeding and Husbandry Support
Citation
When using the B6;129-Rnu2-8^nmf291/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #005048 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for <nmf291>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Rnu2-8nmf291

Allele Symbol: Rnu2-8nmf291

Disease Terms

Research Areas By Phenotype

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

Genotype: Rnu2-8nmf291 related

Mammalian Phenotype Terms by Genotype

Genotype: Rnu2-8nmf291/Rnu2-8nmf291B6;129-Rnu2-8/J

behavior/neurological phenotype

muscle phenotype

nervous system phenotype

Genotype: Rnu2-8nmf291/Rnu2-8nmf291involves: 129S4/SvJae * C57BL/6J

behavior/neurological phenotype

nervous system phenotype

Genotype: Rnu2-8nmf291/Rnu2-8+involves: 129S4/SvJae * C57BL/6J

behavior/neurological phenotype

nervous system phenotype

References

Additional - Rnu2-8nmf291 related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Rnu2-8^nmf291

Allele Symbol: Rnu2-8^nmf291

Genotype: Rnu2-8^nmf291 related

Genotype: Rnu2-8^nmf291/Rnu2-8^nmf291
B6;129-Rnu2-8/J

Genotype: Rnu2-8^nmf291/Rnu2-8^nmf291
involves: 129S4/SvJae * C57BL/6J

Genotype: Rnu2-8^nmf291/Rnu2-8⁺
involves: 129S4/SvJae * C57BL/6J

Additional - Rnu2-8^nmf291 related