Strain Detail Sheet

Phenotype:
Homozygous phenotype: Inflammation of the paws. Viable to at least 12 months age. Splenomegaly. Normal coat.

Heterozygous phenotype: Normal

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

Ptpn6^m1Btlr/Ptpn6^m1Btlr

        C57BL/6-Ptpn6<m1Btlr>/Mmcd

• mortality/aging
  • decreased susceptibility to bacterial infection induced morbidity/mortality (MGI Ref ID J:142845)
    • inoculation with 5x10⁵ CFUs leads to the death of all controls while killing none of the mutant mice
• limbs/digits/tail phenotype
  • ulcerated paws (MGI Ref ID J:142845)
    • plantar surfaces of the feet develop inflamed, raw, weeping lesions in 90% of mice between 10 and 25 weeks of age
    • this inflammation leads to thickening of the epidermis, microabscesses in the epidermal and dermal layers, and a neutrophilic infiltrate in the dermal layer
    • cellularity of the bone marrow adjacent to lesions is increased
    • this phenotype is dependent on the presence of microbes in the housing
• immune system phenotype
  • abnormal myeloid leukocyte morphology (MGI Ref ID J:142845)
    • there are an increased number of myeloid cells in the spleen and bone marrow of mice over 7 weeks of age
    • increased neutrophil cell number (MGI Ref ID J:142845)
      • increased numbers of neutrophils are found in the spleen and bone marrow of mice over 7 weeks of age
  • decreased mature B cell number (MGI Ref ID J:142845)
    • there is a 40%-50% reduction in the number of mature B cells in the peripheral blood and bone marrow
  • decreased susceptibility to bacterial infection (MGI Ref ID J:142845)
    • mice have a diminished bacterial burden 2 and 3 days after inocula tion with Listeria monocytogenes
    • decreased susceptibility to bacterial infection induced morbidity/mortality (MGI Ref ID J:142845)
      • inoculation with 5x10⁵ CFUs leads to the death of all controls while killing none of the mutant mice
  • enlarged spleen (MGI Ref IDs J:142845, J:94077)
    • splenomegaly (MGI Ref ID J:94077)
    • occurs in mice after 6 weeks of age with a mean weight of 98 mg compared to 68 mg (MGI Ref ID J:142845)
    • this phenotype is dependent on the presence of microbes in the housing (MGI Ref ID J:142845)
  • increased IgM level (MGI Ref ID J:142845)
    • mean serum IgM levels are about 2.5 fold higher than in controls
    • this phenotype is dependent on the presence of microbes in the housing
  • increased anti-chromatin antibody level (MGI Ref ID J:142845)
    • significant levels of anti-chromatin IgM (about 6 micrograms/ml) and IgG (3 micrograms/ml) are detectable in the sera of mice over 4 months of age
  • increased inflammatory response (MGI Ref ID J:94077)
    • inflammation of the paws
    • lung inflammation (MGI Ref ID J:142845)
      • the lungs contain hematopoietic cell infiltrates
      • this phenotype is dependent on the presence of microbes in the housing
    • salivary gland inflammation (MGI Ref ID J:142845)
      • salivary glands contain hematopoietic cell infiltrates
      • this phenotype is dependent on the presence of microbes in the housing
• hematopoietic system phenotype
  • abnormal myeloid leukocyte morphology (MGI Ref ID J:142845)
    • there are an increased number of myeloid cells in the spleen and bone marrow of mice over 7 weeks of age
    • increased neutrophil cell number (MGI Ref ID J:142845)
      • increased numbers of neutrophils are found in the spleen and bone marrow of mice over 7 weeks of age
  • decreased mature B cell number (MGI Ref ID J:142845)
    • there is a 40%-50% reduction in the number of mature B cells in the peripheral blood and bone marrow
  • enlarged spleen (MGI Ref IDs J:142845, J:94077)
    • splenomegaly (MGI Ref ID J:94077)
    • occurs in mice after 6 weeks of age with a mean weight of 98 mg compared to 68 mg (MGI Ref ID J:142845)
    • this phenotype is dependent on the presence of microbes in the housing (MGI Ref ID J:142845)
  • increased erythroid progenitor cell number (MGI Ref ID J:142845)
    • increase numbers of erythroid cells are found in the spleen though numbers are reduced in the bone marrow
• respiratory system phenotype
  • lung inflammation (MGI Ref ID J:142845)
    • the lungs contain hematopoietic cell infiltrates
    • this phenotype is dependent on the presence of microbes in the housing
• digestive/alimentary phenotype
  • salivary gland inflammation (MGI Ref ID J:142845)
    • salivary glands contain hematopoietic cell infiltrates
    • this phenotype is dependent on the presence of microbes in the housing
• endocrine/exocrine gland phenotype
  • salivary gland inflammation (MGI Ref ID J:142845)
    • salivary glands contain hematopoietic cell infiltrates
    • this phenotype is dependent on the presence of microbes in the housing
• integument phenotype
  • integument phenotype (MGI Ref ID J:94077)
    • normal coat

Founder genetic background: C57BL/6J

Strain genetic background: C57BL/6J

Strain Development:
G1 father and G2 mother generated G3 progeny. Breed G3 brother-sister mutants to generate G4 progeny. Breed G4 siblings to generate G5 mutants.

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

Primary Reference:

Croker BA; Lawson BR; Berger M; Eidenschenk C; Blasius AL; Moresco EM; Sovath S; Cengia L; Shultz LD; Theofilopoulos AN; Pettersson S; Beutler BA, Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, MyD88, and a microbial trigger., Proc Natl Acad Sci U S A 2008 Sep 30;105(39):15028-33 (Medline PMID: 18806225)

For additional information see: Mutagenetix, a catalog of mutations identified in the Beutler Laboratory at The Scripps Research Institute.

None

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.) Request this Strain
MMRRC Item # Description	Distribution Fee/unit (US $)	Units	Notes
015198-UCD-RESUS Litter recovered from cryo-archive	$2,022.00 Non-Profit	Litter	Recovered litter1; additional fees for any special requests.
015198-UCD-SPERM Cryo-preserved spermatozoa	$437.00 Non-Profit	Aliquot	Approximate quantity.2
015198-UCD-EMBRYO Cryo-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 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.