Strain Detail Sheet

Strain Name    :

FVB.129S4(B6)-Ptpn1tm1Bbk/Mmjax

Stock Number :

032242-JAX

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Ptpn1tm1Bbk
Name: targeted mutation 1, Barabra B Kahn
Alteration at locus: Knockout
Gene Symbol: Ptpn1
Name: protein tyrosine phosphatase, non-receptor type 1
Chromosome: 2
Alteration at locus: Knockout

Genetic Alterations:
A neomycin cassette was inserted into exon 1.

Genotype Determination:

ES Cell Line: J1 derived from 129S4/SvJae

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

Phenotype

Homozygous: Decreased adiposity and insulin sensitivity; resistant to high fat diet-induced obesity.

Heterozygous: normal


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.
Ptpn1tm1Bbk/Ptpn1+
        involves: 129S4/SvJae * C57BL/6J
  • growth/size phenotype
    • abnormal postnatal growth/weight/body size (MGI Ref ID J:63236)
      • male heterozygotes weaned onto a chow diet gain less weight than wild-type males over a 15-week period
      • in contrast, male heterozygotes fed a 55% fat diet gain similar amounts of weight as wild-type males
      • no weight differences are noted in female heterozygotes fed a chow diet for 15 weeks post-weaning
      • decreased body weight (MGI Ref ID J:63236)
        • on a high-fat diet, male heterozygotes weigh on average 10% less than wild-type males
  • homeostasis/metabolism phenotype
    • decreased circulating insulin level (MGI Ref ID J:63236)
      • on a chow diet, serum insulin levels (fasted and fed) of male heterozygotes are similar to those of male homozygotes
      • in contrast, on a high-fat diet, heterozygous serum insulin levels are comparable to those of wild-type mice, suggesting that (on this diet) one copy of the gene is sufficient to mediate its effects on energy expenditure and insulin action
    • decreased circulating leptin level (MGI Ref ID J:63236)
      • on a chow diet, male heterozygotes show an ~60% reduction in fed serum leptin levels relative to wild-type males; a similar reduction is noted in male homozygotes
      • on a high-fat diet, male heterozygotes show an intermediate reduction in fed serum leptin levels relative to wild-type and homozygous mutant males
Ptpn1tm1Bbk/Ptpn1tm1Bbk
        involves: 129/Sv * C57BL/6
  • endocrine/exocrine gland phenotype
    • abnormal pancreatic beta cell morphology (MGI Ref ID J:87249)
      • homozygotes display a reduction in pancreatic cross-sectional beta-cell area relative to wild-type mice
Ptpn1tm1Bbk/Ptpn1tm1Bbk
        involves: 129S4/SvJae * C57BL/6J
  • growth/size phenotype
    • abnormal postnatal growth/weight/body size (MGI Ref ID J:63236)
      • male homozygotes weaned onto a chow diet gain less weight than wild-type males over a 15-week period; this difference becomes significant at 9 weeks post-weaning
      • no weight differences are noted in female homozygotes fed a chow diet for 15 weeks post-weaning
      • decreased body weight (MGI Ref ID J:63236)
        • by 15 weeks post-weaning, male homozygotes fed a chow diet weigh 16% less than wild-type males
        • on a high fat diet, male homozygotes weigh on average 38% less than wild-type males
        • reduced body weight is partly due to decreased lipid content in mutant adipocytes
      • decreased susceptibility to diet-induced obesity (MGI Ref ID J:63236)
        • when fed a 55% fat (caloric content) diet for 4 months, male homozygotes remain lean, with peak weights comparable to those of mutant males on a chow diet
        • female homozygotes fed the high-fat diet also display significantly lower weight gain relative to wild-type females
  • homeostasis/metabolism phenotype
    • abnormal body composition (MGI Ref ID J:63236)
      • decreased percent water in carcass (MGI Ref ID J:63236)
        • on a high fat diet, male homozygotes show a decrease in total carcass water content relative to wild-type
    • abnormal energy expenditure (MGI Ref ID J:63236)
      • on a high fat diet, male homozygotes dissipate excess energy as heat, rather than storing it as fat
      • reduced metabolic efficiency result s in resistance to diet-induced obesity
      • decreased susceptibility to diet-induced obesity (MGI Ref ID J:63236)
        • when fed a 55% fat (caloric content) diet for 4 months, male homozygotes remain lean, with peak weights comparable to those of mutant males on a chow diet
        • female homozygotes fed the high-fat diet also display significantly lower weight gain relative to wild-type females
    • decreased circulating glucose level (MGI Ref ID J:63236)
      • on both a chow and a high-fat diet, male homozygotes display significantly reduced fasting and fed blood glucose levels relative to wild-type males
    • decreased circulating insulin level (MGI Ref ID J:63236)
      • on a chow diet, serum insulin levels (fed but not fasted) of male homozygotes are significantly lower than those of wild-type males
      • on a high-fat diet, serum insulin levels (both fed and fasted) of male homozygotes are significantly lower than those of wild-type males
    • decreased circulating leptin level (MGI Ref ID J:63236)
      • on a chow diet, male homozygotes show a 64% reduction in serum leptin levels relative to wild-type males; notably, serum leptin levels remain low upon high-fat feeding
    • improved glucose tolerance (MGI Ref ID J:63236)
      • chow-fed male homozygotes exhibit an enhanced ability to clear glucose from peripheral circulation during intraperitoneal glucose tolerance tests (GTTs)
      • in contrast, blood glucose levels and GTTs remain unaltered in chow-fed mutant females
    • increased basal metabolism (MGI Ref ID J:63236)
      • on a high fat diet, male homozygotes display a 22% increase in basal metabolic rate relative to wild-type males
    • increased core body temperature (MGI Ref ID J:63236)
      • on a high fat diet, male homozygotes exhibit a significant increase in core body temperature relative to wild-type males
    • increased insulin sensitivity (MGI Ref ID J:63236)
      • chow-fed male (but not female) homozygotes display enhanced insulin sensitivity in insulin tolerance tests; insulin sensitivity remains elevated on a high-fat diet
      • homozygotes show enhanced insulin sensitivity in hyperinsulinemic-euglycemic clamp studies, as shown by notable increases i n rates of whole-body glucose disposal, glycolysis, and nonoxidative glucose metabolism
      • interestingly, insulin sensitivity increases specifically in skeletal muscle, not in white adipose tissue
  • adipose tissue phenotype
    • abnormal fat cell morphology (MGI Ref ID J:63236)
      • male homozygotes show a 2.6-fold decrease in average adipocyte volume; in contrast, adipocyte cell number remains unaffected
    • abnormal fat pad morphology (MGI Ref ID J:63236)
      • on a 55% fat diet, male homozygotes show a 3-fold reduction in subcutaneous fat pad weights relative to wild-type males
      • decreased epididymal fat pad weight (MGI Ref ID J:63236)
        • on a 55% fat diet, male homozygotes show a 3-fold reduction in epididymal fat pad weights relative to wild-type males
      • decreased inguinal fat pad weight (MGI Ref ID J:63236)
        • on a 55% fat diet, male homozygotes show a 3-fold reduction in inguinal fat pad weights relative to wild-type males
      • decreased interscapular fat pad weight (MGI Ref ID J:63236)
        • on a 55% fat diet, male homozygotes show a 3-fold reduction in interscapular fat pad weights relative to wild-type males
    • decreased percent body fat (MGI Ref ID J:63236)
      • on a high fat diet, male homozygotes show a significant reduction in the mass of white fat depots and body lipid content and a smaller reduction in fat-free dry mass
      • notably, homozygotes display normal levels of serum free fatty acids in both the fed and fasted states relative to wild-type mice
    • decreased white adipose tissue amount (MGI Ref ID J:63236)
      • on a chow diet, male homozygotes show a 3-fold reduction in white fat pad mass relative to wild-type mice; brown adipose tissue mass remains unaffected
  • behavior/neurological phenotype
    • abnormal food intake (MGI Ref ID J:63236)
      • male homozygotes tend to display a higher food intake than wild-type mice, but show normal stool mass with no detectable lipids
  • endocrine/exocrine gland phenotype
    • endocrine/exocrine gland phenotype (MGI Ref ID J:63236)
      • on a high fat diet, male homozygotes display normal serum thyroxine (T4) levels relative to wild-type males

Strain of Origin: 129S4/SvJae

Strain genetic background: FVB.129S4

Strain Development: The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6J.  The rusulting hybrids was then backcrossed to FVB/N for 20 generations.

Suggested Control Mice: Wild-type littermates or FVB/N mice

Research Applications

  • Diabetes/Obesity
  • Metabolism

Strain Origin

Donor: Benjamin G. Neel, M.D., Ph.D., Ontario Cancer Institute.

Primary Reference:

Klaman LD, Boss O, Peroni OD, Kim JK, Martino JL, Zabolotny JM, Moghal N, Lubkin M, Kim YB, Sharpe AH, Stricker-Krongrad A, Shulman GI, Neel BG, Kahn BB. Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol Cell Biol. 2000 Aug;20(15):5479-89. (Medline PMID: 10891488)

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 csmmrrc@jax.org.

Appearance

Coat color: White (albino)

Other:

Breeding

MMRRC Breeding System: Backcross or Sib-mating
While maintaining a live colony, these mice are bred as homozygotes.

Breeding Scheme(s):

    Generation: N20+

    Overall Breeding Performance: Excellent

    Reproductive Statistics

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

    Age Reproductive Decline: Variable 12 months

    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
    032242-JAX-RESUSLitter recovered from cryo-archive
    $2,022.00
    Non-Profit
    Litter Recovered litter1; additional fees for any special requests.
    032242-JAX-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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