Strain Detail Sheet

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.

Ptpn1^tm1Bbk/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

Ptpn1^tm1Bbk/Ptpn1^tm1Bbk

        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

Ptpn1^tm1Bbk/Ptpn1^tm1Bbk

        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