Overview

This strain, which combines the n-Tr20^m1J and Gtpbp2^nmf205 mutations, has strong ribosomal stalling in the brain and is valuable for characterizing molecular interactions and pathways involved in protein translation.

The Jackson Laboratory cannot guarantee that cryorecovery of strains from the discontinued NIH-funded Neuroscience Mutagenesis Facility (NMF) will be successful or that the anticipated phenotype or genotype will be obtained. The cryorecovery fee for this effort will not be refunded or prorated if the recovery is unsuccessful or is in any way unsatisfactory. Genotyping will be the responsibility of the Purchaser.

Genetic overview

Genetic Background	Generation

Gtpbp2^nmf205

Allele Type	Gene Symbol	Gene Name
Chemically induced (ENU) (Null/Knockout)	Gtpbp2	GTP binding protein 2

n-TRtct5^m1J

Allele Type	Gene Symbol	Gene Name
Spontaneous (Not Specified)	n-TRtct5	nuclear encoded tRNA arginine 5 (anticodon TCT)

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Research Applications

Neurobiology Research
Cell Biology Research
Sensorineural Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The animals exhibit an unsteady gait, with 'high' hind limbs (walking on hind toes), which can be observed at approximately 4 weeks of age (mean 4.6+/-0.7; n=21, but as early as 3 weeks of age); the impairment progresses over time, i.e. hind limbs become weaker, and the animals show a staggering gait. Because of phenotypic similarities to nmf291, allele tests between nmf205 and nmf291 were performed but did not produce any affected mice.

Standard pathology work-up on four mutants (38 to 51 days of age) revealed loss of cerebellar granule cells in all four animals and cortical laminar necrosis in three animals. Subsequent characterization by Ishimura et al, 2014, revealed that the nmf205 mutation in Gtpbp2 requires the presence of the n-Tr20^m1J point mutation, a strain characteristic of C57BL/6J and C57BL/6JEiJ, in order for the neurodegenerative phenotype to present. The phenotype results from ribosomal stalling at AGA codons, which requires the presence of both mutations for full phenotypic expression. The phenotypic assessment was further characterized and found to include neurodegeneration in the retina including photoreceptor degeneration, and degeneration of amacrine, horizontal, and ganglion cells. Mice die by 8 to 9 weeks of age with progressive neuronal apoptosis. Apoptotic loss is found between 3 and 4 weeks of age the inner granule layer, and between 5 and 8 weeks of age also in the granule cells of the dentate gyrus, CA2 pyramidal neurons, and layer IV cortical neurons.

Development

This phenotypic deviant was generated by ethylnitrosourea (ENU) mutagenesis in C57BL/6J males (Stock No. 000664), in the Neuroscience Mutagenesis facility at The Jackson Laboratory. Mutagenized males were crossed to C57BL/6J females; G3 descendants of the mutagenized males were selected for neurological impairment. In 2004 sperm was cryopreserved from homozygous males then at generation N4F1.

Control Suggestions

Untyped from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Ishimura R; Nagy G; Dotu I; Zhou H; Yang XL; Schimmel P; Senju S; Nishimura Y; Chuang JH; Ackerman SL. 2014. RNA function. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration. Science 345(6195):455-9PubMed: 25061210 MGI: J:211326
JAX Neuroscience Mutagenesis Facility. 2003. Heritable mouse mutants from JAX NMF ENU Mutagenesis Program MGI Direct Data SubmissionMGI: J:82238

View All References

Genetics

Gtpbp2^nmf205

Allele Symbol: Gtpbp2^nmf205

Allele Name	neuroscience mutagenesis facility, 205
Allele Type	Chemically induced (ENU) (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Gtpbp2, GTP binding protein 2
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	17
Molecular Note	This ENU-induced T to C point mutation in the consensus splice donor site of intron 6 results in misspliced mRNAs with premature stop codons. Western blot analysis failed to detect this protein in cerebellar extracts from homozygotes.

n-TRtct5^m1J

Allele Symbol: n-TRtct5^m1J

Allele Name	mutation 1, Jackson
Allele Type	Spontaneous (Not Specified)
Allele Synonym(s)	n-Tr20^C57BL/6J; n-TRtct5^rs4644711-T; rs46447118
Gene Symbol and Name	n-TRtct5, nuclear encoded tRNA arginine 5 (anticodon TCT)
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	1
Molecular Note	This C-to-T transition, the T variant of SNP rs46447118, found in C57BL/6J and C57BL/6JEiJ but not any of the other 18 inbred strains tested, is in nucleotide 50 in the stem of the T loop and impairs maturation, leading to accumulation of a 105 nucleotide pre-tRNA band with leader and trailer sequences instead of the usual 115 nucleotide pre-tRNA, and also diminishes aminoacylation of this isodecoder.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Gtpbp2^nmf205 related

Neurobiology Research
- Cortical Defects
- Neurodegeneration
- Neuroscience Mutagenesis Facility Strain
- Ataxia (Movement) Defects
- Cerebellar Defects
Cell Biology Research
- Protein Processing
Sensorineural Research
- Retinal Degeneration

Mammalian Phenotype Terms by Genotype

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

Genotype: Gtpbp2^nmf205/Gtpbp2^nmf205 n-TRtct5^m1J/n-TRtct5^m1J
C57BL/6J-Gtpbp2/J

behavior/neurological phenotype

abnormal motor capabilities/coordination/movement
- an unsteady gait can be observed in mutant mice at approximately 6-9 weeks of age

ataxia
- truncal ataxia evident at 6 weeks of age

nervous system phenotype

abnormal cerebellar layer morphology

abnormal cerebellum morphology

abnormal dentate gyrus morphology

abnormal hippocampus CA2 region morphology
- increased pyknotic nuclei are found in pyramidal neurons in the CA2 but not CA1 region of the hippocuampus

abnormal horizontal cell morphology

amacrine cell degeneration

decreased cerebellar granule cell number
- progressive apoptosis of inner granule layer neurons is found between 3 and 4 weeks of age

increased neuron apoptosis
- between 3 and 4 weeks of age progressive apoptosis of neurons in the inner granule layer is found, between 5 and 8 weeks of age apoptosis of granule cells in the dentate gyrus, CA2 pyramidal neurons, and layer IV cortical neurons are found, and many neorons in the retina including photoreceptors and amacrine, horizontal, and ganglion cells degenerate during this time
- ns in the retina including photoreceptors and amacrine, horizontal, and ganglion cells degenerate during this time

retinal ganglion cell degeneration

retinal photoreceptor degeneration

vision/eye phenotype

abnormal horizontal cell morphology

abnormal retina morphology
- degeneration of many neurons in the retina occurs by 2 months of age, including photoreceptors, amacrine cells, horizontal cells, and ganglion cells

amacrine cell degeneration

retinal degeneration

retinal ganglion cell degeneration

retinal photoreceptor degeneration

cellular phenotype

abnormal translational elongation
- codons, which is exacerbated in the absence of functional GTPBP2
- the point mutation in n-Tr20 results in decreased levels of processed n-Tr20 and increased levels of immature n-Tr20 over time, particularly in the cerebellum, and the reduction in the available pool of this isodecoder results in ribosomal stalling at AGA codons, which is exacerbated in the absence of functional GTPBP2

increased neuron apoptosis
- between 3 and 4 weeks of age progressive apoptosis of neurons in the inner granule layer is found, between 5 and 8 weeks of age apoptosis of granule cells in the dentate gyrus, CA2 pyramidal neurons, and layer IV cortical neurons are found, and many neorons in the retina including photoreceptors and amacrine, horizontal, and ganglion cells degenerate during this time
- ns in the retina including photoreceptors and amacrine, horizontal, and ganglion cells degenerate during this time

homeostasis/metabolism phenotype

abnormal translational elongation
- codons, which is exacerbated in the absence of functional GTPBP2
- the point mutation in n-Tr20 results in decreased levels of processed n-Tr20 and increased levels of immature n-Tr20 over time, particularly in the cerebellum, and the reduction in the available pool of this isodecoder results in ribosomal stalling at AGA codons, which is exacerbated in the absence of functional GTPBP2

mortality/aging

premature death
- homozygotes die at 8 to 9 weeks of age

Genotype: Gtpbp2^nmf205/Gtpbp2⁺ n-TRtct5^m1J/n-TRtct5^m1J
C57BL/6J-Gtpbp2/J

normal phenotype

no abnormal phenotype detected
- no neurodegeneration was observed

References

Ishimura R; Nagy G; Dotu I; Zhou H; Yang XL; Schimmel P; Senju S; Nishimura Y; Chuang JH; Ackerman SL. 2014. RNA function. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration. Science 345(6195):455-9PubMed: 25061210 MGI: J:211326
JAX Neuroscience Mutagenesis Facility. 2003. Heritable mouse mutants from JAX NMF ENU Mutagenesis Program MGI Direct Data SubmissionMGI: J:82238

Additional - Gtpbp2^nmf205 related

Additional - n-TRtct5^m1J related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Appearance
- black, ataxic (tottering)
  Related Genotype: a/a Gtpbp2^nmf205/Gtpbp2^nmf205
  
  black, unaffected
  Related Genotype: a/a Gtpbp2^nmf205/+ or a/a +/+ or a/a +/?
Citation
When using the C57BL/6J-Gtpbp2^nmf205/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #004823 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
	Unknown for nmf205

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.

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

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Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

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Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Gtpbp2nmf205

Allele Symbol: Gtpbp2nmf205

n-TRtct5m1J

Allele Symbol: n-TRtct5m1J

Disease Terms

Research Areas By Phenotype

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

Genotype: Gtpbp2nmf205 related

Mammalian Phenotype Terms by Genotype

Genotype: Gtpbp2nmf205/Gtpbp2nmf205 n-TRtct5m1J/n-TRtct5m1JC57BL/6J-Gtpbp2/J

behavior/neurological phenotype

nervous system phenotype

vision/eye phenotype

cellular phenotype

homeostasis/metabolism phenotype

mortality/aging

Genotype: Gtpbp2nmf205/Gtpbp2+ n-TRtct5m1J/n-TRtct5m1JC57BL/6J-Gtpbp2/J

normal phenotype

References

Additional - Gtpbp2nmf205 related

Additional - n-TRtct5m1J related

Genotyping Protocols

Appearance

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

Gtpbp2^nmf205

Allele Symbol: Gtpbp2^nmf205

n-TRtct5^m1J

Allele Symbol: n-TRtct5^m1J

Genotype: Gtpbp2^nmf205 related

Genotype: Gtpbp2^nmf205/Gtpbp2^nmf205 n-TRtct5^m1J/n-TRtct5^m1J
C57BL/6J-Gtpbp2/J

Genotype: Gtpbp2^nmf205/Gtpbp2⁺ n-TRtct5^m1J/n-TRtct5^m1J
C57BL/6J-Gtpbp2/J

Additional - Gtpbp2^nmf205 related

Additional - n-TRtct5^m1J related