Strain Detail Sheet

Strain Name    :

C57BL/6J-Gimap5m1Btlr/Mmucd

Stock Number :

030019-UCD

Other Names   :

Sphinx, C57BL/6J-Gimap5m1Btlr/Mmcd

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Gimap5m1Btlr
Name: mutation 1, Bruce Beutler
Alteration at locus: Chemically Induced
Gene Symbol: Gimap5
Name: GTPase, IMAP family member 5
Chromosome: 6
Alteration at locus: Chemically Induced

Genetic Alterations:
The mutation is an ENU-induced G to T transversion at position 352 in exon 3 of the Gimap5 gene.

Genotype Determination:

ES Cell Line: Not Applicable

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

Phenotype

Homozygous phenotype: Sphinx homozygous mice do not have CD8+ T cells or NK cells and there is a progressive decline in B cell and CD4+ T cell numbers. After 6 weeks of age, homozygotes develop progressive normocytic anemia (with increased variation in RBC width and thrombocytopenia), diarrhea and rapid weight loss weight with death between 8 and 12 weeks. Livers acquire an abnormal morphology, with hyperplasia and nodules resembling tumors.

Heterozygous phenotype: Wild-type.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Gimap5m1Btlr/Gimap5m1Btlr
        involves: C57BL/6J
  • mortality/aging
    • premature death (MGI Ref ID J:160090)
      • mice die by 14 weeks of age
      • however, adoptive transfer of wild-type splenocytes reduces early mortality and adoptive transfer of Cd4, Cd8a, or Tcra-J null splenocytes prevents premature death
  • immune system phenotype
    • abnormal B cell physiology (MGI Ref ID J:160090)
      • mice immunized with NP-CGG+alum+LPS or NP-ficoll fail to produce T-dependent antigen-specific IgG1 antibodies or T-independent antigen-specific IgM responses unlike similarly treated wild-type mice
      • abnormal B cell proliferation (MGI Ref ID J:160090)
        • following PMA and ionomycin stimulation, B cells exhibit an increased percentage of B cells in the S phase and fewer in G2 phase compared with similarly treated wild-type cells
        • LPS-stimulated B cells exhibit an increase in percentage of cells in the S phase compared with similarly treated wild-type cells
        • however, proximal mitogenic signaling and cell cycle entry are normal
        • decreased B cell proliferation (MGI Ref ID J:160090)
          • B cells fail to proliferate after BCR stimulation, or treatment with the diacylglycerol mimetic, PMA, and the Ca++ mobilizing agent ionomycin unlike similarly treated wild-type mice
          • however, B cell stimulated with LPS or CD40 exhibit normal proliferation
      • decreased IgG level (MGI Ref ID J:160090)
        • decreased IgG1 level (MGI Ref ID J:160090)
        • decreased IgG2a level (MGI Ref ID J:160090)
          • mice exhibit a trend towards reduced Ig2a serum levels compared with wild-type mice
        • decreased IgG2b level (MGI Ref ID J:160090)
        • decreased IgG3 level (MGI Ref ID J:160090)
      • decreased IgM level (MGI Ref ID J:160090)
    • abnormal NK T cell physiology (MGI Ref ID J:160090)
      • alpha-Gal-Cer-stimulated invariant NK T cells produce no IFN-gamma and TNF-alpha and reduced IL4 compared with wild-type mice
      • however, alpha-Gal-Cer-stimulated invariant NK T cells produce normal amounts of IL13
    • abnormal common lymphocyte progenitor cell morphology (MGI Ref ID J:160090)
      • mice exhibit an increase in common lymphocyte progenitors (CLP) in the liver compared with wild-type mice
      • however, adoptive transfer of wild-type splenocytes reduces splenic CLPs
      • however, the number of common lymphoid progenitors in the bone marrow is normal
    • abnormal response to transplant (MGI Ref ID J:160090)
      • mice immunized with ovalbumin-expressing cells fail to reject adoptively transferred NK cells or CD8+ T cell target cells unlike similarly treated wild-type mice
    • abnormal spleen B cell follicle morphology (MGI Ref ID J:160090)
      • reduced in size and number by P14 with granulocyte accumulation
    • decreased circulating interferon-gamma level (MGI Ref ID J:160090)
      • following alpha-Gal-Cer stimulation
    • decreased circulating interleukin-4 level (MGI Ref ID J:160090)
      • following alpha-Gal-Cer stimulation
    • decreased interferon-gamma secretion (MGI Ref ID J:160090)
      • in alpha-Gal-Cer-stimulated invariant NK T cells
    • decreased interleukin-4 secretion (MGI Ref ID J:160090)
      • in alpha-Gal -Cer-stimulated invariant NK T cells
    • decreased lymphocyte cell number (MGI Ref ID J:160090)
      • mice exhibit lymphopenia unlike wild-type mice
      • decreased B cell number (MGI Ref ID J:160090)
        • splenic B cells are decreased in number compared to in wild-type mice
        • decreased mature B cell number (MGI Ref ID J:160090)
          • the number of mature B cell in the B cell compartment is reduced compared to in wild-type mice
          • however, the percentages of marginal zone B cells and follicular B cells are normal
          • decreased B-1 B cell number (MGI Ref ID J:160090)
      • decreased CD8-positive T cell number (MGI Ref ID J:160090)
        • near absent
      • decreased NK T cell number (MGI Ref ID J:160090)
        • the number of invariant NK T cells is reduced with age unlike in wild-type mice
      • decreased NK cell number (MGI Ref ID J:160090)
        • near absent
    • decreased tumor necrosis factor secretion (MGI Ref ID J:160090)
      • in alpha-Gal-Cer-stimulated invariant NK T cells
    • increased granulocyte number (MGI Ref ID J:160090)
      • mice exhibit an increase in granulocyte numbers in the spleen compared with wild-type mice
      • however, antibiotic treatment prevents accumulation of granulocytes
      • increased neutrophil cell number (MGI Ref ID J:160090)
    • intestinal inflammation (MGI Ref ID J:160090)
      • by 14 weeks, mice exhibit intestinal inflammation unlike wild-type mice
      • treatment with antibiotics ameliorates intestinal inflammation
      • colit is (MGI Ref ID J:160090)
        • after 6 weeks, mice exhibit cell infiltration of the colon unlike wild-type mice
        • after 10 weeks, mice exhibit severe colitis with goblet cell depletion, leukocyte infiltration into the lamina propria, epithelial cell hyperplasia, and crypt loss unlike wild-type mice
    • thymus atrophy (MGI Ref ID J:160090)
      • mice exhibit thymus atrophy with age unlike wild-type mice
      • however, adoptive transfer of wild-type splenocytes rescues thymus atrophy
  • digestive/alimentary phenotype
    • abnormal intestinal epithelium morphology (MGI Ref ID J:160090)
      • after 10 weeks, mice exhibit epithelial cell hyperplasia in the colon unlike in wild-type mice
      • abnormal intestinal goblet cells (MGI Ref ID J:160090)
        • after 10 weeks, mice exhibit goblet cell depletion in the colon unlike in wild-type mice
      • abnormal large intestine crypts of Lieberkuhn morphology (MGI Ref ID J:160090)
        • after 10 weeks, mice exhibit crypt loss in the colon unlike in wild-type mice
    • diarrhea (MGI Ref ID J:160090)
      • after 4 weeks in male mice
    • intestinal inflammation (MGI Ref ID J:160090)
      • by 14 weeks, mice exhibit intestinal inflammation unlike wild-type mice
      • treatment with antibiotics ameliorates intestinal inflammation
      • colitis (MGI Ref ID J:160090)
        • after 6 weeks, mice exhibit cell infiltration of the colon unlike wild-type mice
        • after 10 weeks, mice exhibit severe colitis with goblet cell depletion, leukocyte infiltration into the lamina propria, epithelial cell hyperplasia, and crypt loss unlike wild-type mice
  • liver/biliary system phenotype
    • liver/biliary system phenotype (MGI Ref ID J:160090)
      • in culture, hepatocytes show no growth advantage and no dysplastic liver cells are observed
      • mice exhibit normal liver metabolic function
      • abnormal liver morphology (MGI Ref ID J:160090)
        • mice exhibit extramedullary hematopoiesis in the liver with foci of hematopoietic cells and hyperplastic nodules unlike wild-type mice
  • growth/size phenotype
    • cachexia (MGI Ref ID J:160090)
      • by 14 weeks, mice exhibit wasting unlike wild-type mice
      • however, mice treated with antibiotics or adoptive transfer of wild-type, Cd4, Cd8a, or Tcra-J null splenocytes do not exhibit weight loss
    • postnatal growth retardation (MGI Ref ID J:160090)
      • after 4 weeks in male mice
      • after 6 weeks in female mice, less dramatic than in male mice
  • homeostasis/metabolism phenotype
    • decreased circulating interferon-gamma level (MGI Ref ID J:160090)
      • following alpha-Gal-Cer stimulation
    • decreased circulating interleukin-4 level (MGI Ref ID J:160090)
      • following alpha-Gal-Cer stimulation
  • endocrine/exocrine gland phenotype
    • abnormal large intestine crypts of Lieberkuhn morphology (MGI Ref ID J:160090)
      • after 10 weeks, mice exhibit crypt loss in the colon unlike in wild-type mice
  • hematopoietic system phenotype
    • abnormal bone marrow cell morphology/development (MGI Ref ID J:160090)
      • the number of megakaryocyte/erythroid progenitors in the bone marrow decline with age unlike in wild-type mice
      • the numbers of megakaryocyte/erythroid and granulo-monocyte progenitors are increased in the liver compared to in wild-type mice
      • however, the number of common lymphoid progenitors in the bone marrow is normal
      • abnormal B cell proliferation (MGI Ref ID J:160090)
        • following PMA and ionomycin stimulation, B cells exhibit an increased percentage of B cells in the S phase and fewer in G2 phase compared with similarly treated wild-type cells
        • LPS-stimulated B cells exhibit an increase in percentage of cells in the S phase compared with similarly treated wild-type cells
        • however, proximal mitogenic signaling and cell cycle entry are normal
        • decreased B cell proliferation (MGI Ref ID J:160090)
          • B cells fail to proliferate after BCR stimulation, or treatment with the diacylglycerol mimetic, PMA, and the Ca++ mobilizing agent ionomycin unlike similarly treated wild-type mice
          • however, B cell stimulated with LPS or CD40 exhibit normal proliferation
      • abnormal common lymphocyte progenitor cell morphology (MGI Ref ID J:160090)
        • mice exhibit an increase in common lymphocyte progenitors (CLP) in the liver compared with wild-type mice
        • however, adoptive transfer of wild-type splenocytes reduces splenic CLPs
        • however, the number of common lymphoid progenitors in the bone marrow is normal
      • abnormal common myeloid progenitor cell morphology (MGI Ref ID J:160090)
        • mice exhibit an increase in common myeloid progenitors (CMP) in the liver compared with wild-type mice
        • however, adoptive transfer of wild-type splenocytes reduces splenic CMPs
      • decreased platelet cell number (MGI Ref ID J:160090)
    • abnormal spleen B cell follicle morphology (MGI Ref ID J:160090)
      • reduced in size and number by P14 with granulocyte accumulation
    • anemia (MGI Ref ID J:160090)
      • mice exhibit normocytic anemia unlike wild-type mice
      • however, adoptive transfer of wild-type splenocytes rescues anemia
    • decreased hemoglobin content (MGI Ref ID J:160090)
    • decreased lymphocyte cell number (MGI Ref ID J:160090)
      • mice exhibit lymphopenia unlike wild-type mice
      • decreased B cell number (MGI Ref ID J:160090)
        • splenic B cells are decreased in number compared to in wild-type mice
        • decreased mature B cell number (MGI Ref ID J:160090)
          • the number of mature B cell in the B cell compartment is reduced compared to in wild-type mice
          • however, the percentages of marginal zone B cells and follicular B cells are normal
          • decreased B-1 B cell number (MGI Ref ID J:160090)
      • decreased CD8-positive T cell number (MGI Ref ID J:160090)
        • near absent
      • decreased NK T cell number (MGI Ref ID J:160090)
        • the number of invariant NK T cells is reduced with age unlike in wild-type mice
      • decreased NK cell number (MGI Ref ID J:160090)
        • near absent
    • extramedullary hematopoiesis (MGI Ref ID J:160090)
      • mice exhibit extramedullary hematopoiesis in the liver unlike in wild-type mice
      • however, adoptive transfer of wild-type splenocytes reduces extramedullary hematopoiesis
    • increased granulocyte number (MGI Ref ID J:160090)
      • mice exhibit an increase in granulocyte numbers in the spleen compared with wild-type mice
      • however, antibiotic treatment prevents accumulation of granulocytes
      • increased neutrophil cell number (MGI Ref ID J:160090)
    • increased hematopoietic stem cell number (MGI Ref ID J:160090)
      • hematopoietic stem cells and hematopoietic precursors remained in the adult liver unlike in wild-type mice
    • increased red blood cell distribution width (MGI Ref ID J:160090)
    • thymus atrophy (MGI Ref ID J:160090)
      • mice exhibit thymus atrophy with age unlike wild-type mice
      • however, adoptive transfer of wild-type splenocytes rescues thymus atrophy


The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Gimap5m1Btlr/Gimap5m1Btlr
        either: (involves: BALB/cJ * C57BL/6J) or (involves: C3H/HeN * C57BL/6J) or (C57BL/6J * DBA/2J) or (involves: C57BL/6J * FVB/NJ) or (involves: C57BL/6J * NOD/ShiLtJ)
  • hematopoietic system phenotype
    • extramedullary hematopoiesis (MGI Ref ID J:160090)
      • mice exhibit extramedullary hematopoiesis in the liver with foci of hematopoietic cells and hyperplastic nodules unlike wild-type mice
  • liver/biliary system phenotype
    • abnormal liver morphology (MGI Ref ID J:160090)
      • mice exhibit extramedullary hematopoiesis in the liver with foci of hematopoietic cells and hyperplastic nodules unlike wild-type mice

Strain of Origin: C57BL/6J

Strain genetic background: C57BL/6J

Strain Development: The original mutant mouse was created in C57BL/6J background by ENU mutagenesis. The mutant strain has been maintained by backcrossing and subsequent heterozygote breeding with the same C57BL/6J background.

Suggested Control Mice: Wild-type littermates

Research Applications

  • Apoptosis
  • Cancer
  • Developmental biology
  • Diabetes/obesity
  • Hematology
  • Immunology and inflammation
  • Models for human disease

Strain Origin

Donor: Bruce Beutler, M.D., The Scripps Research Institute, La Jolla, CA

Primary Reference:

  • Barnes MJ, Aksoylar H, Krebs P, Bourdeau T, Arnold CN, Xia Y, Khovananth K, Engel I, Sovath S, Lampe K, Laws E, Saunders A, Butcher GW, Kronenberg M, Steinbrecher K, Hildeman D, Grimes HL, Beutler B, Hoebe K. Loss of T cell and B cell quiescence precedes the onset of microbial flora-dependent wasting disease and intestinal inflammation in Gimap5-deficient mice. J Immunol. 2010 Apr 1;184(7):3743-54. (Medline PMID: 20190135)
  • For additional information, please see: Mutagenetix, a catalog of mutations identified in the Beutler Laboratory at The Scripps Research Institute.

Colony and Husbandry Information

Special Considerations

Homozygotes show post-weaning lethality with a life expectancy of 14 weeks.

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: Black

Other:

Breeding

MMRRC Breeding System: Sib-mated

Breeding Scheme(s):

  • Heterozygous female x Heterozygous male

Generation:

Overall Breeding Performance: Good (heterozygotes)

Reproductive Statistics

Viability and Fertility:FemaleMale
Homozygotes are viable: Reduced Reduced
Homozygotes are fertile: No No
Heterozygotes are fertile: Yes Yes
 
Age Reproductive Decline: Unknown Unknown

Average litter size: 4-6

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
030019-UCD-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.
030019-UCD-SPERMCryo-preserved spermatozoa
$437.00
Non-Profit
Aliquot Approximate quantity.2
030019-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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