Phenotypes associated with this allele

• Allele Symbol: Htr2c^tm2Jke
• Allele Name: targeted mutation 2, Joel K Elmquist
• Allele ID: MGI:5569357
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Htr2c^tm2Jke/Y Tg(Pomc1-cre)16Lowl/0 Gt(ROSA)26Sor^tm14(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+	involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * FVB/N	MGI:5569627
cn2	Htr2c^tm2Jke/Y Tg(Zp3-cre)93Knw/0	involves: 129X1/SvJ * C57BL/6J	MGI:5569622
cn3	Htr2c^tm2Jke/Htr2c^tm2Jke Tg(Pomc-cre/ERT2)#Jke/0	involves: 129X1/SvJ * C57BL/6J	MGI:5569625
cn4	Htr2c^tm2Jke/Y Tg(Pomc-cre/ERT2)#Jke/0	involves: 129X1/SvJ * C57BL/6J	MGI:5569626
cn5	Htr2c^tm2Jke/Y Tg(Pomc1-cre)16Lowl/0	involves: 129X1/SvJ * C57BL/6J * FVB/N	MGI:5569623
cn6	Htr2c^tm2Jke/Htr2c^tm2Jke Tg(Pomc1-cre)16Lowl/0	involves: 129X1/SvJ * C57BL/6J * FVB/N	MGI:5569624

Genotype
MGI:5569627

cn1

• Allelic Composition: Htr2c^tm2Jke/Y; Tg(Pomc1-cre)16Lowl/0; Gt(ROSA)26Sor^{tm14(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * FVB/N

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

nervous system

abnormal nervous system electrophysiology ( J:207704 )

• ability of the serotonin receptor 2C agonist mCPP to depolarized Pomc-expressing neurons is abolished in mutants

Genotype
MGI:5569622

cn2

• Allelic Composition: Htr2c^tm2Jke/Y; Tg(Zp3-cre)93Knw/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

mortality/aging

premature death ( J:207704 )

• a high rate of seizure-induced mortality is observed from 6 weeks through 17 weeks

• Background Sensitivity: with further backcrossing to enrich the C57BL/6J background content, the mortality phenotype is almost eliminated

growth/size/body

increased susceptibility to diet-induced obesity ( J:207704 )

• on an obesogenic (high fat,high sugar) diet, higher rate of obesity is observed compared to controls

behavior/neurological

seizures ( J:207704 )

• mice exhibit seizure-induced death

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:207704 )

• on an obesogenic (high fat,high sugar) diet, higher rate of obesity is observed compared to controls

hyperglycemia ( J:207704 )

• mice show enhanced hyperglycemia incidence when fed an obesogenic (high fat,high sugar) diet

nervous system

seizures ( J:207704 )

• mice exhibit seizure-induced death

Genotype
MGI:5569625

cn3

• Allelic Composition: Htr2c^tm2Jke/Htr2c^tm2Jke; Tg(Pomc-cre/ERT2)#Jke/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

behavior/neurological

increased food intake ( J:207704 )

♀ • daily food intake is increased in chow-fed mice given tamoxifen at 11 weeks and monitored from 12-20 weeks

growth/size/body

growth/size/body region phenotype ( J:207704 )

♀N • mice given tamoxifen at 11 weeks and switched to a high fat, high sugar (HFHS) diet 1 week after exhibit higher body weights after 6 weeks on the HFHS diet

increased body weight ( J:207704 )

♀ • mice given tamoxifen at 11 weeks and switched to a high fat, high sugar (HFHS) diet 1 week later exhibit higher body weights after 6 weeks on the HFHS diet

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:207704 )

♀N • chow-fed mutants receiving tamoxifen at 11 weeks do not show changes in respiratory exchange ratio or physical activity from 12-20 weeks

♀N • tamoxifen-treated mutants that are switched to a high fat, high sugar (HFHS) diet exhibit hyperphagia but do not show a further increase in VO2 and VCO2

increased circulating glucose level ( J:207704 )

♀ • two weeks after tamoxifen treatment, chow-fed mutants have elevated levels

increased circulating glucagon level ( J:207704 )

♀ • two weeks after tamoxifen treatment, chow-fed mutants have elevated levels

increased circulating insulin level ( J:207704 )

♀ • hyperinsulinemia is observed 4 weeks after tamoxifen treatment in chow-fed mutants

increased oxygen consumption ( J:207704 )

♀

Genotype
MGI:5569626

cn4

• Allelic Composition: Htr2c^tm2Jke/Y; Tg(Pomc-cre/ERT2)#Jke/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

growth/size/body

growth/size/body region phenotype ( J:207704 )

♂N • mice given tamoxifen at 11 weeks and switched to a high fat, high sugar (HFHS) diet 1 week later exhibit higher body weights after 6 weeks on the HFHS diet

increased body weight ( J:207704 )

♂ • mice given tamoxifen at 11 weeks and switched to a high fat, high sugar (HFHS) diet 1 week after exhibit higher body weights after 6 weeks on the HFHS diet

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:207704 )

♂N • chow-fed mutants receiving tamoxifen at 11 weeks do not show changes in respiratory exchange ratio or physical activity from 12-20 weeks

♂N • tamoxifen-treated mutants that are switched to a high fat, high sugar (HFHS) diet exhibit hyperphagia but do not show a further increase in VO2 and VCO2

increased circulating glucose level ( J:207704 )

♂ • two weeks after tamoxifen treatment, chow-fed mutants have elevated levels

increased circulating glucagon level ( J:207704 )

♂ • two weeks after tamoxifen treatment, chow-fed mutants have elevated levels

increased circulating insulin level ( J:207704 )

♂ • hyperinsulinemia is observed 4 weeks after tamoxifen treatment in chow-fed mutants

increased oxygen consumption ( J:207704 )

♂

behavior/neurological

increased food intake ( J:207704 )

♂ • daily food intake is increased in chow-fed mice given tamoxifen at 11 weeks and monitored from 12-20 weeks

Genotype
MGI:5569623

cn5

• Allelic Composition: Htr2c^tm2Jke/Y; Tg(Pomc1-cre)16Lowl/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6J * FVB/N

behavior/neurological

increased food intake ( J:207704 )

♂ • daily food intake is elevated relative to controls when fed a regular chow diet; when diet is transitioned to a high fat, high sugar (HFHS) diet for 1 week, food intake is significantly increased relative to controls

♂ • 20 week-old mutants which had been fed an HFHS diet for 12 weeks show a higher food intake compared to controls

♂ • administration of d-flenfluaramine or the more specific serotonin 2C receptor agonist mCPP strongly suppresses food intake in control mice, but mutants are not affected

hyperactivity ( J:207704 )

♂ • total activity due to increased dark cycle activity is increased compared to controls when fed a regular chow diet

♂ • 20 week-old mutants which had been fed an HFHS diet for 12 weeks show increased total physical activity compared to controls; this increase is restricted to the dark phase

♂ • when animals are switched to a high fat high sugar diet for 1 week, physical activity does not increase relative to the chow diet

growth/size/body

growth/size/body region phenotype ( J:207704 )

♂N • when fed a regular chow diet, body weights of mutants are similar to controls at weaning and between 8 and 20 weeks of age

increased body weight ( J:207704 )

♂ • HFHS-fed (high fat, high sugar) animals have significantly increased body weights at 4 weeks after introduction of this diet; at 20 weeks on the HFHS-diet, mutants are 25% heavier than controls due to adiposity

♂ • 20 week-old mutants which had been fed an HFHS diet for 12 weeks have increased body weights compared to controls

increased susceptibility to diet-induced obesity ( J:207704 )

♂ • HFHS-fed (high fat, high sugar) animals have significantly increased body weights at 4 weeks after introduction of this diet

♂ • chow-fed mutants transitioned acutely to HFHS food display similarly increased body weights after 1 week of the new diet

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:207704 )

♂N • on a regular chow diet, mutants and controls have similar respiratory exchange ratios when fed a regular chow diet

♂N • chow-fed or HFHS-fed (high fat, high sugar) animals have similar circulating leptin levels

increased susceptibility to diet-induced obesity ( J:207704 )

♂ • HFHS-fed (high fat, high sugar) animals have significantly increased body weights at 4 weeks after introduction of this diet

♂ • chow-fed mutants transitioned acutely to HFHS food display similarly increased body weights after 1 week of the new diet

increased circulating glucose level ( J:207704 )

♂ • at the beginning of the light phase (7 am), chow-fed mice show modestly higher glucose levels than controls; levels are significantly elevated in postabsorptive (4-5 hour morning-fasted animals) but not in overnight (12-24 h) fasted mice

♂ • high fat, high sugar (HFHS) fed mutants also have elevated glucose levels in the postabsorptive period compared to HFHS-fed controls

hyperglycemia ( J:207704 )

♂

increased circulating glucagon level ( J:207704 )

♂ • higher plasma glucagon levels are detected in postabsorptive chow-fed mutants (4-5 hour morning-fasted); levels are comparable to controls with overnight fasting

♂ • HFHS-fed (high fat, high sugar) animals do not show additionally increased plasma glucagon levels compared to chow-fed mutants

increased circulating insulin level ( J:207704 )

♂ • higher plasma insulin levels are detected in postabsorptive chow-fed mutants (4-5 hour morning-fasted); levels are comparable to controls with overnight fasting

♂ • HFHS-fed (high fat, high sugar) animals have a greater increase in plasma insulin compared to chow-fed mutants

increased energy expenditure ( J:207704 )

♂ • increased energy intake and expenditure are observed when fed a regular chow diet

decreased oxygen consumption ( J:207704 )

♂ • 20 week-old mutants which had been fed an HFHS diet for 12 weeks have lower oxygen consumption relative to body weight compared to controls on the same diet while carbon dioxide production is similar to controls

increased oxygen consumption ( J:207704 )

♂ • VO2 (and VCO2) are increased compared to controls when fed a regular chow diet

♂ • when animals are switched to a high fat high sugar diet for 1 week, oxygen consumption/ C02 production does not increase relative to the chow diet

abnormal respiratory quotient ( J:207704 )

♂ • on the high fat high sugar diet for 1 week, respiratory exchange ratio (RER) is slightly decreased in mutants and controls compared to animals on a regular chow diet, but over a 24 hour period, mutants show a modest increase relative to controls

♂ • 20 week-old mutants which had been fed an HFHS (high fat, high sugar) diet for 12 weeks have a higher RER during the dark phase

insulin resistance ( J:207704 )

♂ • hyperinsulinemic-euglycemic clamp experiments in postabsorptive and overnight-fasted 8-9 week old mice show reduced insulin sensitivity

mortality/aging

mortality/aging ( J:207704 )

♂N • animals are born at Mendelian frequency and show no increased mortality compared to controls

Genotype
MGI:5569624

cn6

• Allelic Composition: Htr2c^tm2Jke/Htr2c^tm2Jke; Tg(Pomc1-cre)16Lowl/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6J * FVB/N

mortality/aging

mortality/aging ( J:207704 )

♀N • animals are born at Mendelian frequency and show no increased mortality compared to controls

growth/size/body

growth/size/body region phenotype ( J:207704 )

♀N • when fed a regular chow diet, body weights of mutants are similar to controls at weaning and between 8 and 20 weeks of age

increased body weight ( J:207704 )

♀ • HFHS-fed (high fat, high sugar) animals have significantly increased body weights at 4 weeks after introduction of this diet; at 20 weeks on the HFHS-diet, mutants are 25% heavier than controls due to adiposity

♀ • 20 week-old mutants which had been fed an HFHS diet for 12 weeks have increased body weights compared to controls

increased susceptibility to diet-induced obesity ( J:207704 )

♀ • HFHS-fed (high fat, high sugar) animals have significantly increased body weights at 4 weeks after introduction of this diet

♀ • chow-fed mutants transitioned acutely to HFHS food display similarly increased body weights after 1 week of the new diet

behavior/neurological

increased food intake ( J:207704 )

♀ • daily food intake is elevated relative to controls when fed a regular chow diet; when diet is transitioned to a high fat, high sugar (HFHS) diet for 1 week, food intake is significantly increased relative to controls

♀ • 20 week-old mutants which had been fed an HFHS diet for 12 weeks show a higher food intake compared to controls

♀ • administration of d-flenfluaramine or the more specific serotonin 2C receptor agonist mCPP strongly suppresses food intake in control mice, but mutants are not affected

hyperactivity ( J:207704 )

♀ • total activity due to increased dark cycle activity is increased compared to controls when fed a regular chow diet

♀ • 20 week-old mutants which had been fed an HFHS diet for 12 weeks show increased total physical activity compared to controls; this increase is restricted to the dark phase

♀ • when animals are switched to a high fat high sugar diet for 1 week, physical activity does not increase relative to the chow diet

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:207704 )

♀N • on a regular chow diet, mutants and controls have similar respiratory exchange ratios when fed a regular chow diet

♀N • chow-fed or HFHS-fed (high fat, high sugar) animals have similar circulating leptin levels

increased susceptibility to diet-induced obesity ( J:207704 )

♀ • HFHS-fed (high fat, high sugar) animals have significantly increased body weights at 4 weeks after introduction of this diet

♀ • chow-fed mutants transitioned acutely to HFHS food display similarly increased body weights after 1 week of the new diet

increased circulating glucose level ( J:207704 )

♀ • at the beginning of the light phase (7 am), chow-fed mice show modestly higher glucose levels than controls; levels are significantly elevated in postabsorptive (4-5 hour morning-fasted animals) but not in overnight (12-24 h) fasted mice

♀ • high fat, high sugar (HFHS) fed mutants also have elevated glucose levels in the postabsorptive period compared to HFHS-fed controls

hyperglycemia ( J:207704 )

♀

increased circulating glucagon level ( J:207704 )

♀ • higher plasma glucagon levels are detected in postabsorptive chow-fed mutants (4-5 hour morning-fasted); levels are comparable to controls with overnight fasting

♀ • HFHS-fed (high fat, high sugar) animals do not show additionally increased plasma glucagon levels compared to chow-fed mutants

increased circulating insulin level ( J:207704 )

♀ • higher plasma insulin levels are detected in postabsorptive chow-fed mutants (4-5 hour morning-fasted); levels are comparable to controls with overnight fasting

♀ • HFHS-fed (high fat, high sugar) animals have a greater increase in plasma insulin compared to chow-fed mutants

increased energy expenditure ( J:207704 )

♀ • increased energy intake and expenditure are observed when fed a regular chow diet

decreased oxygen consumption ( J:207704 )

♀ • 20 week-old mutants which had been fed an HFHS diet for 12 weeks have lower oxygen consumption relative to body weight compared to controls on the same diet while carbon dioxide production is similar to controls

increased oxygen consumption ( J:207704 )

♀ • VO2 (and VCO2) are increased compared to controls when fed a regular chow diet

♀ • when animals are switched to a high fat high sugar diet for 1 week, oxygen consumption/ C02 production does not increase relative to the chow diet

abnormal respiratory quotient ( J:207704 )

♀ • on the high fat high sugar diet for 1 week, respiratory exchange ratio (RER) is slightly decreased in mutants and controls compared to animals on a regular chow diet, but over a 24 hour period, mutants show a modest increase relative to controls

♀ • 20 week-old mutants which had been fed an HFHS (high fat, high sugar) diet for 12 weeks have a higher RER during the dark phase

insulin resistance ( J:207704 )

♀ • hyperinsulinemic-euglycemic clamp experiments in postabsorptive and overnight-fasted 8-9 week old mice show reduced insulin sensitivity