Strain Detail Sheet

Strain Name    :

B6.129S7-Hspa1a/Hspa1btm1Dix/Mmmh

Stock Number :

030411-MU

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:
A 3.1-kb neo gene driven by RNA polymerase II promoter was inserted in place of 11 kb genomic DNA separating 5' end of Hspa1a gene and 3' end of Hspa1b 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

Homozygous: Hspa1a/Hspa1b-/- results in no inducible expression of Hspa1b, genomic instability, and enhanced radiosensitivity when cells from knockout mice are subjected to heat shock. Hspa1a/Hspa1b-/- mice have been shown to have increased mortality from sepsis due to cecal ligation and puncture.

Heterozygous: Unknown


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

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)
      • at birth, mutant mice are on average 12% lighter than wild-type newborns
  • 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 repair (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: 129S7/SvEvBrd-Hprt

          Strain genetic background: C57BL/6J

          Strain Development: Original knockout mouse was created in 129/SvJ and speed congenics performed by Wash. U. Mouse Genetics Core to transfer to C57BL/6 background. Heterozygotes were mated to produce homozygotes which were inbred for 5 generations. Hsp70.1/3 are also known as Hspa1a/a1b and the mutation is identical to that of MMRRC:000371 and MMRRC:000372.

          Strain Genetic Background Validation: A sample from this MMRRC strain was analyzed using the Mouse Universal Genotyping Array (MUGA) and MMRRC computational tools were used to assess the genetic background. A summary of the data can be found here.

          MMRRC StrainReference StrainsGenomic makeup (Mb)
          Strain Name MMRRC ID # Reference 1 Reference 2 Ref 1 Ref 2 Het Unknown
          B6.129S7-Hspa1a/Hspa1btm1Dix/Mmmh MMRRC:030411-MU C57BL/6J 129S7/SvEvBrd(AB2.2) 2566 17 0 1


          Suggested Control Mice:

          Wild-type littermates

Research Applications

  • Apoptosis
  • Cell Biology
  • Immunology and Inflammation
  • Models for Human Disease
  • Research Tools

Strain Origin

Donor: David Dix, Ph.D., United States 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)
  • Singleton KD, Wischmeyer PE. Effects of HSP70.1/3 gene knockout on acute respiratory distress syndrome and the inflammatory response following sepsis. Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L956-61. Epub 2005 Dec 16. (Medline PMID: 16361353)

Colony and Husbandry Information

Special Considerations

None

Health Status Report

For more information about this colony's health status contact mmrrc@missouri.edu

Order Request Information

Availability Level

Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at mmrrc@missouri.edu for more details.

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
030411-MU-HOM-FHomozygous female
030411-MU-HOM-MHomozygous male
$218.00
Non-Profit
Per Mouse The mmrrc@missouri.edu may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
030411-MU-SPERMCryo-preserved spermatozoa
$437.00
Non-Profit
Aliquot Approximate quantity.2

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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