Strain Name:

B6.129S7-Atxn7tm1Hzo/J

Stock Number:

008682

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Heterozygous mice carrying a 266 CAG repeat knock-in from the human ataxin 7 gene exhibit hypoactivity, progressive weight loss, retarded growth after 5 weeks of age, droopy eyelids (ptosis) and receded eyes, visual impairment, ataxia, muscle wasting, curvature of the spine (kyphosis), and tremors which are triggered whenever they initiate movement. Some mice developed myoclonic seizures around 12 weeks of age. Homozygous mice show a gene dosage effect, with their phenotype being more severe and disease progression more rapid, resulting in death around 7-8 weeks of age. These mice may be useful as a model of spinocerebellar ataxia type 7 (SCA7).

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

Type Congenic; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Generation?pN1
Generation Definitions
 
Donating Investigator Huda Zoghbi,   Baylor College of Medicine

Description
Heterozygous mice carrying a 266 CAG repeat knock-in from the human ataxin 7 gene exhibit hypoactivity, progressive weight loss, retarded growth after 5 weeks of age, droopy eyelids (ptosis) and receded eyes, visual impairment, ataxia, muscle wasting, curvature of the spine (kyphosis), and tremors which are triggered whenever they initiate movement. At the terminal stage of the disease, animals became extremely hypokinetic and did not drink nor eat, even when their chow was wetted and placed at the bottom of the cage. Some mice developed myoclonic seizures around 12 weeks of age and many of the heterozygotes die around this age. Homozygous mice show a gene dosage effect, with their phenotype being more severe and disease progression more rapid, resulting in death around 7-8 weeks of age. The heterozygous mice develop retinal degeneration and post-tetanic potentiation (PTP) impairment. The knock-in expression pattern matches that of wildtype mice in the cerebellum, retina, hippocampus and other brain regions with accumulation of the expanded CAG in these tissues. These mice may be useful as a model of spinocerebellar ataxia type 7 (SCA7).

Development
A targeting vector containing 266 CAG repeats amplified from a human patient's gene was used to create a knock-in of mouse exon 3. A selectable cassette containing the neomycin resistance and thymidine kinase genes flanked by two loxP sites was inserted about 2.3 kb downstream of mouse exon 4. The vector was introduced to 129S7/SvEvBrd-Hprt1+-derived AB2.2 embryonic stem (ES) cells. Subsequent electroporation of Cre recombinase into positive ES cell clones excised the floxed fragment. Chimeras were crossed to C57BL/6J for more than ten generations by the donating laboratory. This is line H10.

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).
Spinocerebellar Ataxia 7; SCA7
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Atxn7tm1Hzo/Atxn7+

        involves: 129S7/SvEvBrd * C57BL/6
  • mortality/aging
  • premature death
    • death at 14 to 19 weeks of age   (MGI Ref ID J:82072)
    • mice exhibit normal growth until 5 weeks of age, with little to no weight gain thereafter; mice did not eat or drink during terminal stages prior to death   (MGI Ref ID J:82072)
  • behavior/neurological phenotype
  • ataxia
    • gait ataxia displayed by 8 to 9 weeks of age   (MGI Ref ID J:82072)
  • hypoactivity
    • exhibited at terminal stage prior to death   (MGI Ref ID J:82072)
  • impaired coordination
    • impaired motor coordination in rotarod test   (MGI Ref ID J:82072)
  • myoclonus
    • some mice developed myoclonic seizures around 12 weeks of age   (MGI Ref ID J:82072)
  • muscle phenotype
  • myoclonus
    • some mice developed myoclonic seizures around 12 weeks of age   (MGI Ref ID J:82072)
  • reproductive system phenotype
  • female infertility
    • females were infertile at 8 weeks of age   (MGI Ref ID J:82072)
  • male infertility
    • males showed reduced fertility at 16 weeks of age   (MGI Ref ID J:82072)
  • skeleton phenotype
  • kyphosis   (MGI Ref ID J:82072)
  • vision/eye phenotype
  • blepharoptosis
    • eyes receded and ptosis developed as mice aged   (MGI Ref ID J:82072)
  • decreased retinal photoreceptor cell number
    • loss of ~20% of photoreceptors from outer nuclear layer at 15 weeks of age; retinal dysfunction occurring prior to the loss of photorecptors, cone dysfunction occuring prior to rod dysfunction; accumulation of Sca7 protein, forming microaggregates by 8 weeks of age   (MGI Ref ID J:82072)
  • short photoreceptor outer segment
    • shortening of outer segments   (MGI Ref ID J:82072)
  • thin retinal inner plexiform layer
    • thinning of inner plexiform layer   (MGI Ref ID J:82072)
  • nervous system phenotype
  • abnormal cerebellum morphology
    • progressive accumulation of Sca7 protein, first evident at 5 weeks of age   (MGI Ref ID J:82072)
    • abnormal Purkinje cell morphology
      • cell bodies were observed to be smaller than those of wild-type at 16 wks of age; normal numbers of Purkinje cells and their dendritic arbors are present at 16 wks of age   (MGI Ref ID J:82072)
  • decreased brain size   (MGI Ref ID J:82072)
  • decreased post-tetanic potentiation
    • impaired posttetanic potentiation (PTP)   (MGI Ref ID J:82072)
  • decreased retinal photoreceptor cell number
    • loss of ~20% of photoreceptors from outer nuclear layer at 15 weeks of age; retinal dysfunction occurring prior to the loss of photorecptors, cone dysfunction occuring prior to rod dysfunction; accumulation of Sca7 protein, forming microaggregates by 8 weeks of age   (MGI Ref ID J:82072)
  • myoclonus
    • some mice developed myoclonic seizures around 12 weeks of age   (MGI Ref ID J:82072)
  • short photoreceptor outer segment
    • shortening of outer segments   (MGI Ref ID J:82072)

Atxn7tm1Hzo/Atxn7+

        involves: 129S7/SvEvBrd * C57BL/6J
  • mortality/aging
  • premature death   (MGI Ref ID J:107098)
  • vision/eye phenotype
  • abnormal retinal rod cell morphology
    • rod photoreceptors exhibit chromatin decondensation; rod nuclei contain more euchromatin and show a reduced and disorganized heterochromatin territory   (MGI Ref ID J:107098)
  • nervous system phenotype
  • abnormal retinal rod cell morphology
    • rod photoreceptors exhibit chromatin decondensation; rod nuclei contain more euchromatin and show a reduced and disorganized heterochromatin territory   (MGI Ref ID J:107098)

Atxn7tm1Hzo/Atxn7tm1Hzo

        involves: 129S7/SvEvBrd * C57BL/6
  • mortality/aging
  • premature death
    • death at 7 to 8 weeks of age   (MGI Ref ID J:82072)

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

Atxn7tm1Hzo/Atxn7+

        involves: 129S7/SvEvBrd
  • mortality/aging
  • premature death
    • mutants with 100 CAG repeats exhibit a shorter lifespan than wild-type mice, with an average of 18.7 months   (MGI Ref ID J:179021)
    • mutants with 230 CAG repeats have an average lifespan of only 3.5 months   (MGI Ref ID J:179021)
  • growth/size/body phenotype
  • weight loss
    • in mutants with 100 and 230 CAG repeats   (MGI Ref ID J:179021)
  • behavior/neurological phenotype
  • abnormal motor coordination/ balance
    • gradual loss of mobility in mutants with 100 and 230 CAG repeats   (MGI Ref ID J:179021)
    • ataxia
      • mutants with 100 and 230 CAG repeats progressively develop mild ataxia   (MGI Ref ID J:179021)
  • tremors
    • in mutants with 100 and 230 CAG repeats   (MGI Ref ID J:179021)
  • skeleton phenotype
  • kyphosis
    • in mutants with 100 and 230 CAG repeats   (MGI Ref ID J:179021)
  • vision/eye phenotype
  • blepharoptosis
    • in mutants with 100 and 230 CAG repeats   (MGI Ref ID J:179021)

Atxn7tm1Hzo/Atxn7tm1Hzo

        involves: 129S7/SvEvBrd
  • mortality/aging
  • premature death
    • mutants with 100 CAG repeats die earlier than heterozygotes, with a lifespan averaging 12.1 months   (MGI Ref ID J:179021)
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • mutants with 100 CAG repeats at 7-8 months of age are able to stretch their hindlimbs normally upon tail suspension as in wild-type mice   (MGI Ref ID J:179021)
    • abnormal gait
      • at 8-9 months of age, but not 4 months of age, mutants with 100 CAG repeats walk with a significantly wider hind stance and dispersed fore- and hind-steps relative to wild-type mice   (MGI Ref ID J:179021)
    • ataxia
      • mutants with 100 CAG repeats progressively develop mild ataxia   (MGI Ref ID J:179021)
  • nervous system phenotype
  • abnormal Purkinje cell morphology
    • Purkinje cells of mutants with 100 CAG repeats have smaller soma size, however numbers of Purkinje cells are normal   (MGI Ref ID J:179021)
  • abnormal cerebellum vermis morphology
    • the cerebellar vermis of mutants with 100 CAG repeats shows mild cortical atrophy in the molecular layer of lobules VI, VII, and X at 8-9 months of age   (MGI Ref ID J:179021)
  • retinal photoreceptor degeneration
    • mutants with 100 CAG repeats develop retinal atrophy, first observed at 4 months of age   (MGI Ref ID J:179021)
  • vision/eye phenotype
  • retinal outer nuclear layer degeneration
    • mutants with 100 CAG repeats exhibit normal retinal development, however mild thinning of the retina outer nuclear layer is seen at 4 months of age, and by 8 months of age, the outer nuclear layer is drastically thinner   (MGI Ref ID J:179021)
  • retinal photoreceptor degeneration
    • mutants with 100 CAG repeats develop retinal atrophy, first observed at 4 months of age   (MGI Ref ID J:179021)
View Research Applications

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

Neurobiology Research
Ataxia (Movement) Defects
      Spinocerebellar ataxia
Neuromuscular Defects
Tremor Defects

Sensorineural Research
Eye Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Atxn7tm1Hzo
Allele Name targeted mutation 1, Huda Y Zoghbi
Allele Type Targeted
Common Name(s) Sca7266Q/5Q; Sca7266Q;
Mutation Made By Huda Zoghbi,   Baylor College of Medicine
Strain of Origin129S7/SvEvBrd-Hprt
ES Cell Line NameAB2.2
ES Cell Line Strain129S7/SvEvBrd-Hprt
Promoter Atxn7, ataxin 7, mouse, laboratory
Molecular Note The polyglutamine tract in exon 3 was expanded to 266 CAG repeats via homologous recombination. A single loxP site remained downstream of exon 4. While levels of mutant and wild-type transcript were similar in heterozygous mutant mice, immunostaining of brain tissue indicated increased levels mutant protein. The number of CAG repeats did not decrease by more than 10 (30 nt) in the two lines initially studied. Naturallly occurring contracted mutations of the 266Q tract have been observed, resulting in 230and 100 CAG repeats. [MGI Ref ID J:179021] [MGI Ref ID J:82072]

Genotyping

Genotyping Information

Genotyping Protocols

Atxn7tm1Hzo FML Tg assay, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Atxn7tm1Hzo related

Bowman AB; Yoo SY; Dantuma NP; Zoghbi HY. 2005. Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation. Hum Mol Genet 14(5):679-91. [PubMed: 15661755]  [MGI Ref ID J:96393]

Chen YC; Gatchel JR; Lewis RW; Mao CA; Grant PA; Zoghbi HY; Dent SY. 2012. Gcn5 loss-of-function accelerates cerebellar and retinal degeneration in a SCA7 mouse model. Hum Mol Genet 21(2):394-405. [PubMed: 22002997]  [MGI Ref ID J:179021]

Gatchel JR; Watase K; Thaller C; Carson JP; Jafar-Nejad P; Shaw C; Zu T; Orr HT; Zoghbi HY. 2008. The insulin-like growth factor pathway is altered in spinocerebellar ataxia type 1 and type 7. Proc Natl Acad Sci U S A 105(4):1291-6. [PubMed: 18216249]  [MGI Ref ID J:131821]

Helmlinger D; Hardy S; Abou-Sleymane G; Eberlin A; Bowman AB; Gansmuller A; Picaud S; Zoghbi HY; Trottier Y; Tora L; Devys D. 2006. Glutamine-expanded ataxin-7 alters TFTC/STAGA recruitment and chromatin structure leading to photoreceptor dysfunction. PLoS Biol 4(3):e67. [PubMed: 16494529]  [MGI Ref ID J:107098]

Janer A; Werner A; Takahashi-Fujigasaki J; Daret A; Fujigasaki H; Takada K; Duyckaerts C; Brice A; Dejean A; Sittler A. 2010. SUMOylation attenuates the aggregation propensity and cellular toxicity of the polyglutamine expanded ataxin-7. Hum Mol Genet 19(1):181-95. [PubMed: 19843541]  [MGI Ref ID J:155115]

Kahle JJ; Gulbahce N; Shaw CA; Lim J; Hill DE; Barabasi AL; Zoghbi HY. 2011. Comparison of an expanded ataxia interactome with patient medical records reveals a relationship between macular degeneration and ataxia. Hum Mol Genet 20(3):510-27. [PubMed: 21078624]  [MGI Ref ID J:167231]

Noma S; Ohya-Shimada W; Kanai M; Ueda K; Nakamura T; Funakoshi H. 2012. Overexpression of HGF attenuates the degeneration of Purkinje cells and Bergmann glia in a knockin mouse model of spinocerebellar ataxia type 7. Neurosci Res 73(2):115-21. [PubMed: 22426494]  [MGI Ref ID J:185460]

Yoo SY; Pennesi ME; Weeber EJ; Xu B; Atkinson R; Chen S; Armstrong DL; Wu SM; Sweatt JD; Zoghbi HY. 2003. SCA7 knockin mice model human SCA7 and reveal gradual accumulation of mutant ataxin-7 in neurons and abnormalities in short-term plasticity. Neuron 37(3):383-401. [PubMed: 12575948]  [MGI Ref ID J:82072]

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 & HusbandryWhen maintained as a live colony, heterozygotes may be bred. Male heterozygous mice are reported to have reduced fertility after 8 weeks of age. Female heterozygous mice are said to fail to deliver pups when they are mated after 8 weeks of age.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3300.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $4290.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

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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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