Overview

Also Known As:Sca1^154Q/2Q, Atxn1[154Q]

These mice carry a knock-in mutation of the Atxn1 (formerly Sca1) and exhibit growth retardation, lack of motor coordination, cognitive defects, and muscle wasting, ataxia and an abnormal gait. They nay be useful in studies of neurodegenerative diseases.

Donating Investigator

Huda Zoghbi, Baylor College of Medicine

Genetic overview

Genetic Background	Generation

Atxn1^tm1Hzo

Allele Type	Gene Symbol	Gene Name
Targeted (Inserted expressed sequence)	Atxn1	ataxin 1

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Research Applications

Neurobiology Research
Developmental Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice that are heterozygous for the targeted mutation are viable but have a reduced lifespan (34-40 weeks). The allele consists of a 154 CAG trinucleotide repeat unit placed within exon 8 of the targeted endogenous mouse locus. Modified transcripts and protein can be detected in brain tissue. By 8 weeks of age, mutant mice exhibit noticeable growth retardation. Progressive neurological degeneration initiates by 9 weeks of age, when mutant mice begin to exhibit a clasping phenotype when held by the tail. By 20 weeks of age muscle wasting, ataxia and an abnormal gait are observed. A lack of motor coordination is detected via an accelerating rotarod test by 5 to 7 weeks. Cognitive defects include poor spatial learning performance and reduced Pavlovian conditioned fear response (impaired memory). Hippocampal basal synaptic function is impaired. Immunohistochemical and immunofluorescent analysis of brain tissue reveals neuronal intranuclear inclusions by 6 weeks of age. Older animals exhibit decreased brain weight, reduced dendritic arborization and loss of Purkinje cells. The onset and progression of the phenotype observed in these mutant mice mimics many of the features of spinaocerebellar ataxia type 1 (SCA1) and my be useful in SCA1- and neurodegenerative disease- related studies.

Development

A targeting vector containing sequence of an expanded repeat of 154 CAGs and a floxed (loxP site flanked) neomycin resistance selection cassette was used to disrupt exon 8. The construct was electroporated into 129S7/SvEvBrd-Hprt^b-m2 derived AB2.2 embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the selection cassette. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to the same for 10 generations.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Watase K; Weeber EJ; Xu B; Antalffy B; Yuva-Paylor L; Hashimoto K; Kano M; Atkinson R; Sun Y; Armstrong DL; Sweatt JD; Orr HT; Paylor R; Zoghbi HY. 2002. A long CAG repeat in the mouse Sca1 locus replicates SCA1 features and reveals the impact of protein solubility on selective neurodegeneration. Neuron 34(6):905-19PubMed: 12086639 MGI: J:77225

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Genetics

Atxn1^tm1Hzo

Allele Symbol: Atxn1^tm1Hzo

Allele Name	targeted mutation 1, Huda Y Zoghbi
Allele Type	Targeted (Inserted expressed sequence)
Allele Synonym(s)	Atx1-KI; atxn1^154Q; Sca1^154Q/2Q; Sca1^154Q; Sca1-KI
Gene Symbol and Name	Atxn1, ataxin 1
Gene Synonym(s)
Promoter	Atxn1, ataxin 1, mouse, laboratory
Strain of Origin	129S7/SvEvBrd-Hprt^b-m2
Chromosome	13
Molecular Note	An expanded tract of 154 CAG repeats was engineered and knocked into exon 8. Additionally, a floxed neo-TK cassette was inserted into the upstream intron and subsequently deleted in ES cells via cre mediated recombination. While equivalent transcript levels were identified in both mutant and wild-type mice by RT-PCR, reduced levels of mutant protein were observed in brain tissue. The authors attributed this apparent reduction in protein level to an increased difficulty of extraction or solubilization due to the mutant protein accumulating into nuclear aggregates as mice age.

Disease/Phenotype

Disease Terms

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).

spinocerebellar ataxia type 1

Research Areas By Phenotype

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

Neurobiology Research
- Ataxia (Movement) Defects
- Behavioral and Learning Defects
- Cerebellar Defects
  - Purkinje cell defect
Developmental Biology Research
- Growth 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: Atxn1^tm1Hzo/Atxn1⁺
involves: 129S7/SvEvBrd * C57BL/6

growth/size/body region phenotype

slow postnatal weight gain
- growth retardation starts at 8 weeks of age
- mice weigh 20% less than wild-type littermates by 11 weeks of age

cachexia
- mice start losing weight after 20 weeks of age

mortality/aging

premature death
- premature death first occurs between 35 to 45 weeks of age
- none of the mice survive past 50 weeks of age

muscle phenotype

muscle degeneration
- atrophy of lower limb muscles occurs by 30 weeks of age
- muscle wasting is evident by 20 weeks of age

nervous system phenotype

decreased brain weight
- brain weight is significantly reduced by 16 weeks of age

abnormal Purkinje cell dendrite morphology
- there is a reduction in dendritic arbor of cerebellar Purkinje neurons from mice 6 to 11 weeks of age
- this reduction in dendritic arbor leads to a reduction in membrane capacitance

neuronal intranuclear inclusions
- ubiquitinated neuronal intranuclear inclusions (NI) are present in CA1 hippocampal neurons by 7 weeks of age
- NI are also present in cortical neurons and thalamic nuclei by 7 weeks of age
- NI are present in numerous parts of the brain during the endstage of disease

decreased Purkinje cell number
- significantly fewer Purkinje cells are present in 40-week old mice compared to wild-type littermates

dilated brain ventricles
- all ventricles are dilated by 40 weeks of age

reduced long term potentiation
- hippocampus LTP is significantly reduced in 24 week old mice

abnormal excitatory postsynaptic potential
- EPSP magnitude is significantly decreased in the hippocampus 90 minutes after high-frequency stimulation

skeleton phenotype

kyphosis
- is observed by 30 weeks of age

behavior/neurological phenotype

ataxia
- evident by 20 weeks of age

abnormal spatial learning
- 7-8 week old mice take more time and swim further to locate a hidden platform in a morris water test regardless of trial number
- 7-8 week old mice take more time and swim further to locate a submerged but visible platform in a morris water test during the first 6 trials
- Normal - mice perform as wells as wild-type controls in later trials

abnormal gait
- evident by 20 weeks of age

limb grasping
- mice have a clasping phenotype when lifted by the tail starting at 9 weeks of age

impaired coordination
- retention time in a rotarod test is impaired by about half for both 5 and 7 week old mice

abnormal cued conditioning behavior
- in a context fear test, mice display significantly less freezing to the conditioned stimulus 24 hours after the training period but not 1 hour after

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

Genotype: Atxn1^tm1Hzo/Atxn1⁺
B6.129S7-Atxn1

behavior/neurological phenotype

abnormal associative learning
- impaired fear conditioning

impaired coordination
- on a rotarod and dowel test
- mice exhibit increased latency to cross a dowel rod and walk off the rod fewer times than wild-type mice

ataxia

hypoactivity
- in an open field test

nervous system phenotype

neuronal intranuclear inclusions

decreased Purkinje cell number

growth/size/body region phenotype

decreased body weight

mortality/aging

premature death
- Normal - however, exercise improves survival
- mice exhibit premature lethality
- mice die before 60 weeks of age

References

Watase K; Weeber EJ; Xu B; Antalffy B; Yuva-Paylor L; Hashimoto K; Kano M; Atkinson R; Sun Y; Armstrong DL; Sweatt JD; Orr HT; Paylor R; Zoghbi HY. 2002. A long CAG repeat in the mouse Sca1 locus replicates SCA1 features and reveals the impact of protein solubility on selective neurodegeneration. Neuron 34(6):905-19PubMed: 12086639 MGI: J:77225

Additional - Atxn1^tm1Hzo related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Laragen
- Standard PCR:Atxn1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice are bred as heterozygotes. The Donating Investigator indicates that it is best to use male carrier mice in breeding strategies because the allele appears less stable in female mutants. Additionally, the phenotype of homozygous mice is too severe for successful breeding.
- Additional Breeding and Husbandry Support
Citation
When using the Sca1^154Q/2Q, Atxn1[154Q] mouse strain in a publication, please cite the originating article(s) and include JAX stock #005601 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 wild type for Atxn1<tm1Hzo>/

Related Products and Services

Frozen Mouse Embryo	B6.129S-Atxn1<tm1Hzo>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129S-Atxn1<tm1Hzo>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129S-Atxn1<tm1Hzo>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6.129S-Atxn1<tm1Hzo>/J Frozen Embryos	$3373.50

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

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Sca1154Q/2Q, Atxn1[154Q]

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Atxn1tm1Hzo

Allele Symbol: Atxn1tm1Hzo

Disease Terms

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).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Atxn1tm1Hzo/Atxn1+involves: 129S7/SvEvBrd * C57BL/6

growth/size/body region phenotype

mortality/aging

muscle phenotype

nervous system phenotype

skeleton phenotype

behavior/neurological phenotype

Genotype: Atxn1tm1Hzo/Atxn1+B6.129S7-Atxn1

behavior/neurological phenotype

nervous system phenotype

growth/size/body region phenotype

mortality/aging

References

Additional - Atxn1tm1Hzo 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

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Also Known As:Sca1^154Q/2Q, Atxn1[154Q]

Atxn1^tm1Hzo

Allele Symbol: Atxn1^tm1Hzo

Genotype: Atxn1^tm1Hzo/Atxn1⁺
involves: 129S7/SvEvBrd * C57BL/6

Genotype: Atxn1^tm1Hzo/Atxn1⁺
B6.129S7-Atxn1

Additional - Atxn1^tm1Hzo related