Overview

Tardbp^Q101X ENU-induced mutant mice possess a nonsense mutation in exon 3 of the Tardbp gene. These mutant mice may be useful in studying the effects of TDP-43 protein regulation on the development of amyotrophic lateral sclerosis and frontotemporal dementia.

Donating Investigator

Elizabeth MC Fisher, UCL Institute of Neurology

Genetic overview

Genetic Background	Generation

Tardbp^m1H

Allele Type	Gene Symbol	Gene Name
Chemically induced (ENU) (Hypomorph)	Tardbp	TAR DNA binding protein

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Research Applications

Research Tools
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

These Tardbp^Q101X ENU-induced mutant mice possess a nonsense mutation in exon 3 of the TAR DNA binding protein (Tardbp) gene.
The Tardbp gene product, TDP-43, is a protein localized to the nucleus of nerve cells. Ubiquinated accumulations of mutant TDP-43 have been linked to the development of Lou Gehrig's disease (Amyotrophic lateral sclerosis; ALS) and frontotemporal dementia (FTD). Heterozygotes are viable and fertile, homozygotes are embryonic lethal by E6.5. The mutant allele produces a truncated transcript, although no truncated protein is detected. Interestingly, heterozygous mutant mice produce the same amount of wildtype TDP-43 protein as non-mutant-controls (the Tardbp gene is subject to autoregulation mechanisms), yet they exhibit a mild loss-of-function phenotype and behavioral abnormalities. Female mice display a hindlimb limb-clasp defect, with an average onset of 61 weeks, with no abnormal hindlimb neuromuscular function. Males and females also exhibit an abnormal, softer abdominal body tone.

Development

Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder male C57BL/6J mice, a forward genetic screen was utilized to identify mice with a mutation in the TAR DNA binding protein (Tardbp) gene. Males were bred with C3H/HeH females and sperm from F1 males was screened for mutations in Tardbp. A mutation was mapped with Sanger sequencing and a C to T transition in exon 3 of Tardbp resulting in a glutamine to Stop codon nonsense mutation (Q101X). Sperm from Tardbp^Q101X F1 males was used for in vitro fertilization of C57BL/6J oocytes. These Tardbp^Q101X mice were bred to C57BL/6J mice for at least 10 times prior to their arrival at The Jackson Laboratory, where they were further bred to C57BL/6J (Stock No. 000664) for at least one generation.

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Ricketts T; McGoldrick P; Fratta P; de Oliveira HM; Kent R; Phatak V; Brandner S; Blanco G; Greensmith L; Acevedo-Arozena A; Fisher EMC. 2014. A nonsense mutation in mouse Tardbp affects TDP43 alternative splicing activity and causes limb-clasping and body tone defects. PLoS One 9(1):e85962PubMed: 24465814 MGI: J:211620

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Genetics

Tardbp^m1H

Allele Symbol: Tardbp^m1H

Allele Name	mutation 1, Harwell
Allele Type	Chemically induced (ENU) (Hypomorph)
Allele Synonym(s)	Tardbp^Q101X
Gene Symbol and Name	Tardbp, TAR DNA binding protein
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	4
Molecular Note	ENU mutagenesis induced a C to T transition in exon 3 that results in the amino acid substitution of a glutamine to Stop codon nonsense mutation (Q101X).

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis: Production of Chemical Mutations
Neurobiology Research
- Amyotrophic Lateral Sclerosis (ALS)
- Behavioral and Learning Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Tardbp^m1H/Tardbp^m1H
involves: C3H/HeH * C57BL/6J

mortality/aging

embryonic lethality, complete penetrance
- mice die prior to E6.5

Genotype: Tardbp^m1H/Tardbp⁺
involves: C3H/HeH * C57BL/6J

behavior/neurological phenotype

limb grasping
- Normal - however, male mice did not exhibit this phenotype but were not assessed beyond 52 weeks of age
- in female at 61 weeks

mammalian phenotype

nervous system phenotype
- Normal - mice exhibit normal neuromuscular junctions in the abdomen and hindlimbs

muscle phenotype

abnormal muscle tone
- soft abdominal body tone in male and female mice

impaired muscle relaxation
- in the extensor digitorum longus

References

Ricketts T; McGoldrick P; Fratta P; de Oliveira HM; Kent R; Phatak V; Brandner S; Blanco G; Greensmith L; Acevedo-Arozena A; Fisher EMC. 2014. A nonsense mutation in mouse Tardbp affects TDP43 alternative splicing activity and causes limb-clasping and body tone defects. PLoS One 9(1):e85962PubMed: 24465814 MGI: J:211620

Additional - Tardbp^m1H related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Tardbp
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664). Homozygous mice are embryonic lethal prior to E6.5.
- Additional Breeding and Husbandry Support
Citation
When using the B6(C3H)-Tardbp^m1H/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #019899 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 or wildtype for Tardbp<m1H>

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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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General Terms and Conditions

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Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Tardbpm1H

Allele Symbol: Tardbpm1H

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tardbpm1H/Tardbpm1Hinvolves: C3H/HeH * C57BL/6J

mortality/aging

Genotype: Tardbpm1H/Tardbp+involves: C3H/HeH * C57BL/6J

behavior/neurological phenotype

mammalian phenotype

muscle phenotype

References

Additional - Tardbpm1H 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

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Tardbp^m1H

Allele Symbol: Tardbp^m1H

Genotype: Tardbp^m1H/Tardbp^m1H
involves: C3H/HeH * C57BL/6J

Genotype: Tardbp^m1H/Tardbp⁺
involves: C3H/HeH * C57BL/6J

Additional - Tardbp^m1H related