Phenotypes associated with this allele

• Allele Symbol: Ptpn1^tm1Bbk
• Allele Name: targeted mutation 1, Barabra B Kahn
• Allele ID: MGI:2384135
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ptpn1^tm1Bbk/Ptpn1^tm1Bbk	involves: 129S4/SvJae * C57BL/6J	MGI:3583800
hm2	Ptpn1^tm1Bbk/Ptpn1^tm1Bbk	involves: 129/Sv * C57BL/6	MGI:3583982
ht3	Ptpn1^tm1Bbk/Ptpn1^+	involves: 129S4/SvJae * C57BL/6J	MGI:3583815
cx4	Irs2^tm1Mfw/Irs2^tm1Mfw Ptpn1^tm1Bbk/Ptpn1^tm1Bbk	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3583981

Genotype
MGI:3583800

hm1

• Allelic Composition: Ptpn1^tm1Bbk/Ptpn1^tm1Bbk
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

growth/size/body

abnormal body composition ( J:63236 )

decreased percent water in carcass ( J:63236 )

♂ • on a high fat diet, male homozygotes show a decrease in total carcass water content relative to wild-type

abnormal postnatal growth/weight/body size ( 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 ( 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 ( 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

decreased circulating glucose level ( 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 ( 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 ( 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

increased core body temperature ( J:63236 )

♂ • on a high fat diet, male homozygotes exhibit a significant increase in core body temperature relative to wild-type males

abnormal energy expenditure ( J:63236 )

• on a high fat diet, male homozygotes dissipate excess energy as heat, rather than storing it as fat

• reduced metabolic efficiency results in resistance to diet-induced obesity

decreased susceptibility to diet-induced obesity ( 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

improved glucose tolerance ( 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 insulin sensitivity ( 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 in rates of whole-body glucose disposal, glycolysis, and nonoxidative glucose metabolism

• interestingly, insulin sensitivity increases specifically in skeletal muscle, not in white adipose tissue

increased basal metabolism ( J:63236 )

♂ • on a high fat diet, male homozygotes display a 22% increase in basal metabolic rate relative to wild-type males

adipose tissue

decreased white adipose tissue amount ( 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

abnormal fat cell morphology ( 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 ( 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 ( 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 ( 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 ( 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/body weight ( 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

behavior/neurological

abnormal food intake ( 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 glands

endocrine/exocrine gland phenotype ( J:63236 )

♂N • on a high fat diet, male homozygotes display normal serum thyroxine (T4) levels relative to wild-type males

Genotype
MGI:3583982

hm2

• Allelic Composition: Ptpn1^tm1Bbk/Ptpn1^tm1Bbk
• Genetic Background: involves: 129/Sv * C57BL/6

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:87249 )

• homozygotes display a reduction in pancreatic cross-sectional beta-cell area relative to wild-type mice

Genotype
MGI:3583815

ht3

• Allelic Composition: Ptpn1^tm1Bbk/Ptpn1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

growth/size/body

abnormal postnatal growth/weight/body size ( 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 ( J:63236 )

♂ • on a high-fat diet, male heterozygotes weigh on average 10% less than wild-type males

homeostasis/metabolism

decreased circulating insulin level ( 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 ( 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

Genotype
MGI:3583981

cx4

• Allelic Composition: Irs2^tm1Mfw/Irs2^tm1Mfw; Ptpn1^tm1Bbk/Ptpn1^tm1Bbk
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:87249 )

• some double homozygous males survive for as long as 9 months; in contrast, Irs2^tm1Mfw homozygous males are severely diabetic and die around 15 weeks

growth/size/body

decreased body weight ( J:87249 )

• at 6 weeks, double homozygous males weigh 20% less than Irs2^tm1Mfw males

• by 15 weeks, Irs2^tm1Mfw males are severly diabetic and the difference in body weight becomes almost undetectable

homeostasis/metabolism

hyperglycemia ( J:87249 )

• at 15 weeks, double homozygotes exhibit fasting hyperglycemia

impaired glucose tolerance ( J:87249 )

• double homozygous males display improved glucose tolerance and delayed onset of diabetes relative to Irs2^tm1Mfw homozygous males

• however, double homozygotes still exhibit significant glucose intolerance at 6 and 15 weeks

increased insulin sensitivity ( J:87249 )

• at 6 weeks, young double homozygotes show increased peripheral insulin sensitivity; however, peripheral insulin sensitivity is reduced at 15 weeks

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:87249 )

• double homozygotes exhibit increased pancreatic cross-sectional beta-cell area relative to Irs2^tm1Mfw mice

pancreatic islet hyperplasia ( J:87249 )

• double homozygotes exhibit increased pancreatic islet size relative to Irs2^tm1Mfw mice

• despite compensatory islet growth and improved beta-cell function, double homozygotes develop diabetes at 15 weeks