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Strain Detail Sheet


Strain Name: C57BL/6-Dnajc3tm8663Wcl/Mmmh

Stock Number: 010323-MU

Other Names:

Gene Details:

Allele Symbol: Dnajc3tm8663Wcl
Name: DnaJ (Hsp40) homolog, subfamily C, member 3 / targeted mutation 8663, Warren C Ladiges
Alteration at locus: Targeted Mutation

Genetic Alterations:
A mouse C57BL/6 genomic DNA library (Genome Systems, Inc.) in the pBeloBAC11 vector was screened using a restriction fragment probe corresponding to nucleotides -100 to +360 of the mouse P58^IPK cDNA. Based upon preliminary Southern blot analyses, a 15 kb HpaI fragment was subcloned, restriction mapped, and partially sequenced. This sequence was then assembled into an eGFP/ -galactosidase/PKG-Neo/pA targeting vector designed to replace P58^IPK exon 1 containing the translation start site. The targeting vector was transfected into C57BL/6-derived embryonic stem cells.

Genotype Determination:

ES Cell Line: Not applicable

Strain Description

Phenotype:
Homozygous phenotype: Adult male P58^IPK null mice display glucosuria, hyperglycemia, and hypoinsulinemia. P58^IPK null mice show pancreatic cell depletion. Pancreatic cell failure in P58^IPK null mice is associated with increased apoptosis and upregulation of genes associated with apoptosis. P58^IPK null male mice are smaller and can be easily distinguished from heterozygous and wild type mice as early as two weeks of age.

Heterozgyous phenotype: None identified.

Mammalian Phenotype Terms:
      assigned by genotype

Dnajc3tm8663Wcl/Dnajc3tm8663Wcl
        C57BL/6-Dnajc3/Mmmh
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:98194)
    • homozygous null males have an average life span of 14.5 months compared to 25 months in wildtype, while females live longer although life span has not been determined
  • growth/size phenotype
  • decreased body size (MGI Ref ID J:98194)
    • homozygous null mice are smaller as early as 2 weeks of age, and growth curves show that body weights increase in parallel over time but never catch up to that of heterozygotes or wildtype
    • decreased body weight (MGI Ref ID J:98194)
  • adipose tissue phenotype
  • decreased percent body fat (MGI Ref ID J:98194)
    • 10-12 month old homozygous null males have an average of 7% body fat compared to 34% in wildtype
  • homeostasis/metabolism phenotype
  • hyperglycemia (MGI Ref ID J:98194)
    • higher serum glucose levels, however homozygous null mice are not insulin resistant
  • increased circulating insulin level (MGI Ref ID J:98194)
  • increased urine glucose level (MGI Ref ID J:98194)
    • at 4 months of age, began to increase water intake with subsequent increase in urination and evidence of glucosuria, however no evidence of urine ketones
  • renal/urinary system phenotype
  • increased urine glucose level (MGI Ref ID J:98194)
    • at 4 months of age, began to increase water intake with subsequent increase in urination and evidence of glucosuria, however no evidence of urine ketones
  • endocrine/exocrine gland phenotype
  • abnormal pancreatic beta cell morphology (MGI Ref ID J:98194)
    • cytoplasmic atrophy and collapse within the pancreatic islets and multifocal areas of cytoplasmic clefts and apoptotic bodies were seen in islets of 6-month old homozygous null males, however no differences in acini or other parenchyma
    • decreased pancreatic beta cell mass (MGI Ref ID J:98194)
      • the mass of insulin-producing cells was significantly decreased in islets
    • decreased pancreatic beta cell number (MGI Ref ID J:98194)
      • insulin-producing beta cells, but not glucagons producing cells, were greatly depleted in pancreatic islets that was associated with increased apoptosis in islets
  • behavior/neurological phenotype
  • abnormal food intake (MGI Ref ID J:98194)
    • increased consumption of food (4.4 grams of food per gram of body weight compared to 2.8 and 3 grams of food per gram body weight in wildtype and heterozygotes, respectively)

Strain Type:

Founder genetic background: C57BL/6

Strain genetic background: C57BL/6

Strain Development:
The contribution of these stem cells to the germline of chimeric mice was assessed by breeding with C57BL/6 females and screening for black offspring. Heterozygous mice were identified by PCR and intercrossed to obtain a Mendelian ratio of homozygous offspring. Routine genotyping for homozygosity was done by PCR using primers specific for an internal targeting deletion sequence (flanking the 59 bp Xmal deletion in the targeted P58^IPK allele) and an external genomic sequence. Mice were 100% C57BL/6 (from a C57BL/6 ES cell line), and were maintained on the C57BL/6 background by alternate generation backcrossing. Tissues and embryonic fibroblasts derived from homozygous, heterozygous, and wild-type littermates were processed and subjected to Western blot analysis. All progeny displayed the expected Mendelian ratio of heterozygous versus homozygous genotypes.

Research Applications

Strain Origin

Donor: Warren C. Ladiges, DVM, University of Washington

Primary Reference:

Ladiges WC, Knoblaugh SE, Morton JF, Korth MJ, Sopher BL, Baskin CR, MacAuley A, Goodman AG, LeBoeuf RC, Katze MG. Pancreatic beta-cell failure and diabetes in mice with a deletion mutation of the endoplasmic reticulum molecular chaperone gene P58IPK. Diabetes. 2005 Apr;54(4):1074-81. (Medline PMID: 15793246)

Special Considerations

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on the resuscitated animals.

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:

Please complete the MMRRC Conditions of Use (COU) and provide it at the time your order is placed. Note: The preceding link is to the COU text only; the COU user form will be provided after order submission.

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
010323-MU-RESUSLitter recovered from cryo-archive
$2,022.00Non-Profit
$4,109.00For-Profit
Litter Recovered litter1; additional fees for any special requests.
010323-MU-SPERMCryo-preserved spermatozoa
$437.00Non-Profit
$817.00For-Profit
Aliquot Approximate quantity.2

Control Mice:

  • Wildtype littermates

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 breedable 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 contains sufficient material (volume and concentration) for at least two IVF or several artificial inseminations (based on our procedures). The MMRRC makes no guarantee concerning 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 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 (207) 288-6009 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to information.


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Last Modified: June 23, 2010