Strain Detail Sheet

Strain Name    :

B6;129S7-Hspa1a/Hspa1btm1Dix/Mmucd

Stock Number :

000371-UCD

Other Names   :

Hsp70, Hspa1a/a1b neo [B6/129], B6;129S7-Hspa1a/Hspa1btm1Dix/Mmcd, B6;129S5-Hspa1atm1Dix Hspa1btm1Dix/Ucd , B6;129S5-Hspa1a/Hspa1btm1Dix/Ucd

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Hspa1a/Hspa1btm1Dix
Name: targeted mutation 1, David J Dix
Chromosome: 17
Alteration at locus: Knockout
Gene Symbol: Hspa1a
Name: heat shock protein 1A
Chromosome: 17
Alteration at locus: Knockout
Gene Symbol: Hspa1b
Name: heat shock protein 1B
Chromosome: 17
Alteration at locus: Knockout

Genetic Alterations:
Homologous recombination resulted in a 12 kb deletion of both Hspa1a and Hspa1b coding regions, and insertion of a neomycin resistance gene.

Genotype Determination:

ES Cell Line: AB2.2 derived from 129S7/SvEvBrd-Hprt

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

Phenotype

Homozygotes are fertile and generally healthy, but multiple tissues and cells are more susceptible various stressors


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Hspa1a/Hspa1btm1Dix/Hspa1a/Hspa1btm1Dix
        involves: 129S7/SvEvBrd * C57BL/6
  • nervous system phenotype
    • neurofibrillary tangles (MGI Ref ID J:164904)
      • at 32 weeks
    • tau protein deposits (MGI Ref ID J:164904)
Hspa1a/Hspa1btm1Dix/Hspa1a/Hspa1btm1Dix
        involves: 129S7/SvEvBrd * C57BL/6
  • nervous system phenotype
    • neurofibrillary tangles (MGI Ref ID J:164904)
      • at 32 weeks
    • tau protein deposits (MGI Ref ID J:164904)


The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Hspa1a/Hspa1btm1Dix/Hspa1a/Hspa1btm1Dix
        involves: 129S7/SvEvBrd
  • growth/size phenotype
    • decreased birth weight (MGI Ref ID J:87581)
      • mice were 12% lighter than wild-type at birth
  • cellular phenotype
    • abnormal cell physiology (MGI Ref ID J:87581)
      • in vitro oncogenic transformation assays indicate a higher frequency of spontaneous transformants in mutant cells than in wild-type cells
      • whereas heat treatment has no effect on spontaneous cellular transformation and very little effect on ionizing radiation (IR)-induced transformation in wild-type cells, heat has a profound effect on both spontaneous and IR-induced transformation in mutant cells
      • abnormal DNA r epair (MGI Ref ID J:87581)
        • mutant cells treated with heat plus ionizing radiation (IR) exhibit more S-phase-specific chromosomal aberrations at metaphase than cells treated with IR only, suggesting a defect in S-phase-specific DNA repair
      • abnormal cell cycle checkpoint function (MGI Ref ID J:87581)
        • after IR treatment, asynchronously growing mutant MEFs display less inhibition of DNA synthesis than wild-type cells
        • however, transfection of the Hspa1b gene rescues the radioresistant DNA synthesis observed in mutant MEFs
      • decreased cell proliferation (MGI Ref ID J:87581)
        • in culture, both early- and late-passage mutant MEFs display significantly slower growth kinetics than wild-type MEFs
        • mutant MEFs show a 4-fold decrease in plating efficiency relative to wild-type MEFs
      • decreased mitotic index (MGI Ref ID J:87581)
        • after heat treatment (43

          Strain of Origin: C57BL/6NCrl and 129S6/SvEvTac

          Strain genetic background: C57BL/6x129S7

          Suggested Control Mice: Wild-type littermates

Research Applications

  • Apoptosis
  • Cancer
  • Cardiovascular
  • Cell Biology
  • Developmental Biology
  • Immunology and Inflammation
  • Models for Human Disease
  • Neurobiology
  • Reproduction

Strain Origin

Donor: David Dix, Ph.D., U.S. Environmental Protection Agency

Primary Reference:

  • Hunt CR, Dix DJ, Sharma GG, Pandita RK, Gupta A, Funk M, Pandita TK. Genomic instability and enhanced radiosensitivity in Hsp70.1- and Hsp70.3-deficient mice. Mol Cell Biol. 2004 Jan;24(2):899-911. (Medline PMID: 14701760)
  • Hampton CR, Shimamoto A, Rothnie CL, Griscavage-Ennis J, Chong A, Dix DJ, Verrier ED, Pohlman TH. HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts. Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H866-74. Epub 2003 Apr 24. (Medline PMID: 12714332)
  • Schmitt E, Parcellier A, Gurbuxani S, Cande C, Hammann A, Morales MC, Hunt CR, Dix DJ, Kroemer RT, Giordanetto F, Jaattela M, Penninger JM, Pance A, Kroemer G, Garrido C. Chemosensitization by a non-apoptogenic heat shock protein 70-binding apoptosis-inducing factor mutant. Cancer Res. 2003 Dec 1;63(23):8233-40. (Medline PMID: 14678980)

Colony and Husbandry Information

Special Considerations

None.

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@ucdavis.edu.

Appearance

Coat color: Various

Other:

Breeding

MMRRC Breeding System: Sib-mating

Breeding Scheme(s):

  • Homozygous female x Homozygous male littermate

Generation: N2F14 As of: 11/2004

Overall Breeding Performance: Good

Reproductive Statistics

Viability and Fertility:FemaleMale
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes

Age Reproductive Decline: Unknown Unknown

Average litter size: 10

Recommended wean age: 3 weeks

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Conditions of Distribution [Including applicable technology transfer agreements]

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # - Description Distribution
Fee/unit (US $)
Units Notes
000371-UCD-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.
000371-UCD-SPERMCryo-preserved spermatozoa
$437.00
Non-Profit
Aliquot Approximate quantity.2
000371-UCD-EMBRYOCryo-preserved embryos
$1,038.00
Non-Profit
Aliquot Approximate quantity3: 20-40 embryos / aliquot

1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

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