Phenotypes associated with this allele

• Allele Symbol: Pparg⁺
• Allele Name: wild type
• Allele ID: MGI:2152810
• Summary: 18 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Pparg^tm1b(KOMP)Wtsi/Pparg^+	C57BL/6N-Pparg^tm1b(KOMP)Wtsi/H	MGI:5757543
ht2	Pparg^tm1Lja/Pparg^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3580111
ht3	Pparg^tm2(tTA)Yba/Pparg^+	involves: 129S1/SvImJ * C57BL/6	MGI:3784503
ht4	Pparg^tm3(tTA)Yba/Pparg^+	involves: 129S1/SvImJ * C57BL/6	MGI:3784504
ht5	Pparg^tm1Avp/Pparg^+	involves: 129S2/SvPas * C57BL/6	MGI:3695903
ht6	Pparg^tm1Uls/Pparg^+	involves: 129S2/SvPas * C57BL/6	MGI:3055152
ht7	Pparg^tm1Rev/Pparg^+	involves: 129S4/SvJae * C57BL/6J	MGI:2174989
ht8	Pparg^tm1Mae/Pparg^+	involves: 129S6/SvEvTac * C57BL/6	MGI:3050152
ht9	Pparg^tm1.1Unc/Pparg^+	involves: 129S6/SvEvTac * C57BL/6J	MGI:4412012
ht10	Pparg^tm1Tka/Pparg^+	involves: C57BL/6 * CBA	MGI:3818949
ht11	Pparg^tm1Tka/Pparg^+	involves: C57BL/6 * CBA * ICR	MGI:3818960
ht12	Pparg^tm1Wwah/Pparg^+	Not Specified	MGI:3575675
cn13	Ctnnb1^tm2Kem/Ctnnb1^tm2Kem Pparg^tm1.1(tTA)Jmgr/Pparg^+ Tg(tetO-cre)1Jaw/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5581951
cn14	Ctnnb1^tm2Kem/Ctnnb1^+ Pparg^tm1.1(tTA)Jmgr/Pparg^+ Tg(tetO-cre)1Jaw/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5581952
cn15	Ctnnb1^tm2Kem/Ctnnb1^tm2Kem Pparg^tm1.1(tTA)Jmgr/Pparg^+ Tg(tetO-cre)1Jaw/0 Tg(tetO-HIST1H2BJ/GFP)47Efu/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1	MGI:5581950
cn16	Ctnnb1^tm1Mmt/Ctnnb1^+ Pparg^tm1.1(tTA)Jmgr/Pparg^+ Tg(tetO-cre)1Jaw/0	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6	MGI:5581956
cx17	Lep^ob/Lep^ob Pparg^tm1Avp/Pparg^+	involves: 129S2/SvPas * C57BL/6	MGI:3695904
cx18	Atp2b2^m1Mae/Atp2b2^+ Pparg^tm2Mae/Pparg^+	involves: 129S6/SvEvTac * C57BL/6J	MGI:3641270

Genotype
MGI:5757543

ht1

• Allelic Composition: Pparg^{tm1b(KOMP)Wtsi}/Pparg⁺
• Genetic Background: C57BL/6N-Pparg^{tm1b(KOMP)Wtsi}/H
• Cell Lines: EPD0395_2_A02

Data Sources

IMPC Data for Pparg

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

adipose tissue

increased total body fat amount ( J:211773 )

♂

IMPC - HAR

behavior/neurological

abnormal gait ( J:211773 )

♀

IMPC - HAR

growth/size/body

decreased lean body mass ( J:211773 )

♂

IMPC - HAR

homeostasis/metabolism

increased fasting circulating glucose level ( J:211773 )

IMPC - HAR

Genotype
MGI:3580111

ht2

• Allelic Composition: Pparg^tm1Lja/Pparg⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

Hepatic steatosis in Pparg^tm1Lja/Pparg⁺ mice

adipose tissue

decreased body fat mass ( J:98786 )

• reduced fat mass

abnormal brown fat cell morphology ( J:98786 )

• brown adipocytes contained large multiloculated fat vacuoles not present in wild-type

decreased white fat cell size ( J:98786 )

• epididymal white adipose tissue contained a heterogeneous population of adipocytes with mostly small and medium sized cells, compared to the homozygous population of large adipocytes in wild-type

abnormal epididymal fat pad morphology ( J:98786 )

• reduced epididymal white adipose tissue depots

lipodystrophy ( J:98786 )

• exhibited lipodystrophy

growth/size/body

decreased body fat mass ( J:98786 )

• reduced fat mass

decreased body weight ( J:98786 )

• heterozygous mutants gained less weight on a standard or high fat diet than wild-type after 3 months of age, however no differences in food intake or oxygen consumption

homeostasis/metabolism

increased circulating insulin level ( J:98786 )

• males on a high-fat diet exhibited basal hyperinsulinemia

increased circulating free fatty acids level ( J:98786 )

• exhibited higher serum free fatty acid levels on a standard diet than wild-type

insulin resistance ( J:98786 )

• males on a high-fat diet exhibited insulin resistance, as evidenced by lower glucose infusion rates and impaired glucose uptake in skeletal muscle during clamp studies

decreased circulating adiponectin level ( J:98786 )

• significantly lower levels of serum adiponectin levels than in wild-type on either a standard or high fat diet

increased liver triglyceride level ( J:98786 )

• hepatic triglyceride levels were 1.8-fold greater on a standard diet and 1.46-fold greater on a high-fat diet compared to wild-type

muscle

decreased skeletal muscle cell glucose uptake ( J:98786 )

• males on a high-fat diet display impaired glucose uptake in skeletal muscle during clamp studies

liver/biliary system

increased liver triglyceride level ( J:98786 )

• hepatic triglyceride levels were 1.8-fold greater on a standard diet and 1.46-fold greater on a high-fat diet compared to wild-type

macrovesicular hepatic steatosis ( J:98786 )

• 5 month old males exhibited macrovesicular fatty changes in midzonal and centrilobular locations

microvesicular hepatic steatosis ( J:98786 )

• 5 month old males exhibited microvesicular fatty changes around the central vein

cardiovascular system

hypertension ( J:98786 )

• females, but not males, were overtly hypertensive on either the standard or high-fat diet

cellular

decreased skeletal muscle cell glucose uptake ( J:98786 )

• males on a high-fat diet display impaired glucose uptake in skeletal muscle during clamp studies

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
abdominal obesity-metabolic syndrome		DOID:0060611	OMIM:PS605552	J:98786

Genotype
MGI:3784503

ht3

• Allelic Composition: Pparg^tm2(tTA)Yba/Pparg⁺
• Genetic Background: involves: 129S1/SvImJ * C57BL/6

Lipodystrophy phenotypes of Pparg^tm2(tTA)Yba/Pparg⁺ mice

reproductive system

reduced fertility ( J:125992 )

• Background Sensitivity: mice exhibit poor fecundity after introgression onto a C57BL/6 background

adipose tissue

adipose tissue phenotype ( J:125992 )

N • despite the development of dyslipidemia and severe insulin resistance, mice do not develop steatosis or type 2 diabetes

abnormal brown adipose tissue morphology ( J:125992 )

• mice exhibit hypertrophy and unilocular lipid deposition in mutant brown adipocytes

• however, defects can be prevented by midgestational administration of doxycycline and reverted by a 6 week treatment with doxycycline

increased brown fat cell size ( J:125992 )

• mice exhibit hypertrophy in mutant brown adipocytes

• however, defects can be prevented by midgestational administration of doxycycline and reverted by a 6 week treatment with doxycycline

decreased gonadal fat pad weight ( J:125992 )

• gonadal fat pads are severely reduced compared to in wild-type mice

• however, defects can be prevented by midgestational administration of doxycycline and reverted by a 6 week treatment with doxycycline

increased interscapular fat pad weight ( J:125992 )

• mice exhibit 'buffalo humps' comprised of swollen interscapular fat pads due to hypertrophy and unilocular lipid deposition in mutant brown adipocytes

• however, defects can be prevented by midgestational administration of doxycycline and reverted by a 6 week treatment with doxycycline

abnormal white adipose tissue morphology ( J:125992 )

• fibrotic white adipose tissue stroma is filled with fragmented lipid droplets and leukocytes

• remaining adipocytes have irregular shapes and range in size from overtly hypertrophic to minuscule cells

• however, defects were prevented by midgestational administration of doxycycline but adipocyte size does not revert following treatment with doxycycline

absent subcutaneous adipose tissue ( J:125992 )

• mice lack subcutaneous adipocytes

abnormal white fat cell morphology ( J:125992 )

• remaining adipocytes have irregular shapes

abnormal white fat cell size ( J:125992 )

• remaining adipocytes range in size from overtly hypertrophic to minuscule cells

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:125992 )

N • despite the development of dyslipidemia and severe insulin resistance, mice do not develop steatosis or type 2 diabetes

hyperglycemia ( J:125992 )

• hyperglycemia develops prepuberty then normalizes latter in life with only sporadic and transient hyperglycemia

• however, treatment with doxycycline reverses metabolic anomalies

increased circulating insulin level ( J:125992 )

• mice exhibit an increase in serum insulin

• however, treatment with doxycycline reverses metabolic anomalies

increased circulating cholesterol level ( J:125992 )

• mice exhibit an increase in serum cholesterol with early onset

• however, treatment with doxycycline reverses metabolic anomalies

increased circulating free fatty acids level ( J:125992 )

• mice exhibit an increase in serum free fatty acids with early onset

• however, treatment with doxycycline reverses metabolic anomalies

increased circulating triglyceride level ( J:125992 )

• mice exhibit an increase in serum triglycerides with early onset

• however, treatment with doxycycline reverses metabolic anomalies

impaired glucose tolerance ( J:125992 )

• mice exhibit severe glucose intolerance

• however, treatment with doxycycline reverses metabolic anomalies

insulin resistance ( J:125992 )

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:125992 )

• mice exhibit pancreas islet cell hyperplasia

• however, treatment with doxycycline reverses metabolic anomalies

pancreas hyperplasia ( J:125992 )

• mice as old as 12 to 18 months exhibit hyperplasia with intact and insulin-laden pancreatic islets with hyperinsulinemia and normoglycemia

liver/biliary system

enlarged liver ( J:125992 )

• liver size is increased by 60% to 150% and is accompanied by hepatocyte hypertrophy and vacuolization

• however, lipid droplet accumulation is not observed

abnormal hepatocyte morphology ( J:125992 )

• mice exhibit hepatocyte hypertrophy and vacuolization

integument

absent subcutaneous adipose tissue ( J:125992 )

• mice lack subcutaneous adipocytes

growth/size/body

pancreas hyperplasia ( J:125992 )

• mice as old as 12 to 18 months exhibit hyperplasia with intact and insulin-laden pancreatic islets with hyperinsulinemia and normoglycemia

enlarged liver ( J:125992 )

• liver size is increased by 60% to 150% and is accompanied by hepatocyte hypertrophy and vacuolization

• however, lipid droplet accumulation is not observed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital generalized lipodystrophy type 2		DOID:0111136	OMIM:269700	J:125992
familial partial lipodystrophy		DOID:0050440	OMIM:PS151660	J:125992

Genotype
MGI:3784504

ht4

• Allelic Composition: Pparg^tm3(tTA)Yba/Pparg⁺
• Genetic Background: involves: 129S1/SvImJ * C57BL/6

Mild lipodystrophy with modest metabolic anomalies in Pparg^tm3(tTA)Yba/Pparg⁺ mice compared to Pparg^tm2(tTA)Yba/Pparg⁺ mice

adipose tissue

decreased subcutaneous adipose tissue amount ( J:125992 )

• subcutaneous fat pad is reduced but present

• however, treatment with doxycycline reverses defects observed

abnormal brown adipose tissue morphology ( J:125992 )

• brown adipocytes are pale, unilocular and hypertrophic

• however, no buffalo humps are observed and treatment wit doxycycline reverses defects observed

• authors state that defects in brown adipose tissue are the same as in Pparg^tm2Yba heterozygotes

abnormal brown fat cell morphology ( J:125992 )

• brown adipocytes are pale, unilocular and hypertrophic

• however, treatment with doxycycline reverses defects observed

increased brown fat cell size ( J:125992 )

• brown adipocytes are hypertrophic

decreased gonadal fat pad weight ( J:125992 )

• gonadal fat pads are reduced compared to in wild-type mice

• however, treatment with doxycycline reverses defects observed

homeostasis/metabolism

increased circulating insulin level ( J:125992 )

• however, treatment with doxycycline reverses defects observed

• insulin levels are elevated compared to those in wild-type mice but not as high as in Pparg^tm2Yba heterozygotes

increased circulating triglyceride level ( J:125992 )

• triglyceride levels are elevated compared to those in wild-type mice but not as high as in Pparg^tm2Yba heterozygotes

• however, treatment with doxycycline reverses defects observed

liver/biliary system

enlarged liver ( J:125992 )

• the liver is modestly increased in size compared to in wild-type mice

• however, treatment with doxycycline reverses defects observed

integument

decreased subcutaneous adipose tissue amount ( J:125992 )

• subcutaneous fat pad is reduced but present

• however, treatment with doxycycline reverses defects observed

growth/size/body

enlarged liver ( J:125992 )

• the liver is modestly increased in size compared to in wild-type mice

• however, treatment with doxycycline reverses defects observed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital generalized lipodystrophy type 2		DOID:0111136	OMIM:269700	J:125992
familial partial lipodystrophy		DOID:0050440	OMIM:PS151660	J:125992

Genotype
MGI:3695903

ht5

• Allelic Composition: Pparg^tm1Avp/Pparg⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

cellular

abnormal fat cell differentiation ( J:116568 )

• in vitro differentiation of preadipocytes is impaired

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:116568 )

N • on a normal chow or high fat diet insulin sensitivity is similar to wild-type mice unlike human patients with the same mutation

decreased circulating adiponectin level ( J:116568 )

• reduced serum adiponectin level

abnormal lipid homeostasis ( J:116568 )

• impaired clearance of triglycerides and fatty acids in an oral lipid load test

abnormal triglyceride level ( J:116568 )

increased circulating triglyceride level ( J:116568 )

• in mice on a high fat diet

growth/size/body

growth/size/body region phenotype ( J:116568 )

N • on a normal chow or high fat diet body mass is similar to wild-type mice unlike human patients with the same mutation

increased liver weight ( J:116568 )

• in mice on a high fat diet compared to wild-type mice on the same diet

adipose tissue

abnormal adipose tissue distribution ( J:116568 )

• decreased ratio of gonadal white adipose tissue to inguinal subcutaneous white adipose tissue; however total body fat is similar to wild-type

abnormal fat cell differentiation ( J:116568 )

• in vitro differentiation of preadipocytes is impaired

liver/biliary system

increased liver weight ( J:116568 )

• in mice on a high fat diet compared to wild-type mice on the same diet

hepatic steatosis ( J:116568 )

• on a high fat diet but not when fed a normal chow diet

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	familial partial lipodystrophy	DOID:0050440	OMIM:PS151660	J:116568

Genotype
MGI:3055152

ht6

• Allelic Composition: Pparg^tm1Uls/Pparg⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

adipose tissue

decreased total body fat amount ( J:92826 )

• males but not females are resistant to monosodium glutamate-induced increased total body fat

growth/size/body

postnatal growth retardation ( J:92826 )

• modest growth retardation that is exacerbated by monosodium glutamate treatment is seen in male but not female heterozygotes

Genotype
MGI:2174989

ht7

• Allelic Composition: Pparg^tm1Rev/Pparg⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

homeostasis/metabolism

abnormal glucose homeostasis ( J:60354 )

increased insulin sensitivity ( J:60354 )

• male heterozygotes are apparently healthy and exhibit no significant differences in body weight, fat-pad, basal fasting glucose and insulin levels or FFA levels relative to wild-type mice

• unexpectedly, during oral glucose tolerance tests, heterozygotes are able to maintain wild-type glucose levels, despite a significant reduction in plasma insulin concentrations

• during glucose clamp experiments, heterozygotes show a 30% increase in the insulin-induced glucose disposal rate relative to wild-type mice

• similarly, heterozygotes exhibit a significant increase in insulin-induced suppression of hepatic glucose production relative to wild-type mice

• improved insulin sensitivity may be associated with increased serum leptin levels, as heterozygotes do show a significant increase in leptin mRNA expression

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	familial partial lipodystrophy	DOID:0050440	OMIM:PS151660	J:60354

Genotype
MGI:3050152

ht8

• Allelic Composition: Pparg^tm1Mae/Pparg⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

adipose tissue

abnormal adipose tissue distribution ( J:91362 )

• interscapular brown adipose tissue and gonadal fat mass are reduced to about 80% and 70% wild-type, respectively, however the inguinal fat pad and pectoral subcutaneous fat pad are each increased to about 140% wild-type

• the overall ratio of intra-abdominal to extra-abdominal fat weight is reduced to 63% wild-type

abnormal fat cell morphology ( J:91362 )

• the size of adipocytes is abnormally uniform with fewer small cells found

abnormal gonadal fat pad morphology ( J:91362 )

• gonadal fat mass is reduced to about 70% wild-type as a result of a decrease in cell numbers

abnormal inguinal fat pad morphology ( J:91362 )

• the inguinal fat pad is increased to about 140% wild-type

cardiovascular system

hypertension ( J:91362 )

• blood pressure is increased about 8 mmHg in both male and female mutants

endocrine/exocrine glands

abnormal endocrine pancreas morphology ( J:91362 )

• islet area and endocrine mass are significantly increased in mutants fed a high fat diet

homeostasis/metabolism

improved glucose tolerance ( J:91362 )

• glucose tolerance is improved and insulin sensitivity is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	familial partial lipodystrophy	DOID:0050440	OMIM:PS151660	J:91362

Genotype
MGI:4412012

ht9

• Allelic Composition: Pparg^tm1.1Unc/Pparg⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

cardiovascular system

decreased systemic arterial blood pressure ( J:154767 )

• in females at 4 months of age

• overall, increased Pparg expression correlates with decreased blood pressure

Genotype
MGI:3818949

ht10

• Allelic Composition: Pparg^tm1Tka/Pparg⁺
• Genetic Background: involves: C57BL/6 * CBA

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:98823 )

• mice die after the 37th week following treatment with MNU due to gastric tumors

homeostasis/metabolism

decreased susceptibility to diet-induced obesity ( J:58222 )

• when fed a high fat diet, mice do not gain as much weight as similarly treated wild-type mice

• however, when fed a high carbohydrate diet mice gain as much weight as wild-type mice and treatment with pioglitazone restores high fat diet-induced obesity

decreased circulating insulin level ( J:58222 )

• when fed a high fat diet compared to similarly treated wild-type mice

• however, treatment with pioglitazone increases insulin levels when mice are fed a high fat diet

increased circulating leptin level ( J:58222 )

• when fed a high fat diet, leptin serum levels are 1.8-fold higher than in similarly treated wild-type mice

increased body temperature ( J:58222 )

• when fed a high fat diet

increased insulin sensitivity ( J:58222 )

• when fed a high fat diet, mice exhibit insulin sensitivity instead of insulin resistance as do similarly treated wild-type mice

• however, treatment with pioglitazone decreases insulin sensitivity when mice are fed a high fat diet

increased susceptibility to xenobiotic induced morbidity/mortality ( J:98823 )

• mice die after the 37th week following treatment with MNU due to gastric tumors

increased incidence of tumors by chemical induction ( J:98823 )

• following treatment with MNU, mice develop gastric cancer (in 17 of 19 mice) of with 1 is a carcinoma in, 15 are well-differentiated adenocarcinomas, 1 is a moderately differentiated adenocarcinoma and 1 is a lymphoma compared to similarly treated wild type mice that develop gastric carcinoma (in 5 of 9 mice) all of which are well-differentiated adenocarcinomas

• unlike in wild-type mice, treatment with troglitazone does no inhibit MNU-induced carcinogenesis

abnormal response to injury ( J:103209 )

• following pressure overload, mice exhibit increased cardiac hypertrophy and increased interventricular septum and left ventricular posterior wall thickness compared to in similarly treated wild-type mice

• however, treatment of pressure overloaded mice with pioglitazone reduces cardiac hypertrophy

skeleton

skeleton phenotype ( J:89250 )

N • despite increased osteoblast number and bone formation, osteoclast physiology is normal and mice exhibit normal bone loss following ovariectomy

abnormal osteoblast differentiation ( J:89250 )

• osteoblastgenesis is increased compared to in wild-type mice

• in vitro, osteoblastgenesis from bone marrow progenitors is increased compared to in wild-type mice

• however, calvarial osteoblasts, which are more mature than bone marrow cells, exhibit normal morphology and physiology

abnormal bone marrow morphology ( J:89250 )

• at 8 weeks and 52 weeks of age, the number of adipocytes within the bone marrow is lower than in wild-type mice

increased osteoblast cell number ( J:89250 )

• the numbers of osteoblast surface and osteoid surface are doubled compared to in wild-type mice

increased trabecular bone mass ( J:89250 )

• at 8 weeks and 52 weeks of age, trabecular bone mass is increased 40% compared to in wild-type mice

abnormal bone ossification ( J:89250 )

• bone formations is twice as much as in wild-type mice due to increased numbers of osteoblasts

adipose tissue

decreased brown adipose tissue amount ( J:58222 )

• when fed a high fat diet, brown adipose tissue mass is decreased 40% compared to in similarly treated wild-type mice

decreased total body fat amount ( J:58222 )

• when fed a high fat diet, mice exhibit a more than 70% inhibition in the increase in white adipose tissue mass observed similarly treated wild-type mice

• however, treatment with pioglitazone results in increased adipose tissue when fed a high fat diet

abnormal fat cell morphology ( J:58222 , J:89250 )

• when fed a high fat diet, adipocyte size is less than in similarly treated wild-type mice (J:58222)

• when fed a high fat diet, brown adipose tissue adipocytes are 36% smaller than in similarly treated wild-type mice (J:58222)

• however, treatment with pioglitazone increases adipocyte size when mice are fed a high fat diet (J:58222)

• at 8 weeks and 52 weeks of age, the number of adipocytes within the bone marrow is lower than in wild-type mice (J:89250)

cellular

abnormal cell differentiation ( J:58222 )

• 50% fewer embryonic fibroblasts differentiate into adipose cells compared to wild-type embryonic fibroblast cells

• however, pioglitazone partially rescued adipocyte differentiation

abnormal osteoblast differentiation ( J:89250 )

• osteoblastgenesis is increased compared to in wild-type mice

• in vitro, osteoblastgenesis from bone marrow progenitors is increased compared to in wild-type mice

• however, calvarial osteoblasts, which are more mature than bone marrow cells, exhibit normal morphology and physiology

behavior/neurological

decreased food intake ( J:58222 )

• when fed a high fat diet

growth/size/body

decreased susceptibility to diet-induced obesity ( J:58222 )

• when fed a high fat diet, mice do not gain as much weight as similarly treated wild-type mice

• however, when fed a high carbohydrate diet mice gain as much weight as wild-type mice and treatment with pioglitazone restores high fat diet-induced obesity

liver/biliary system

decreased susceptibility to diet-induced hepatic steatosis ( J:58222 )

• when fed a high fat diet

neoplasm

increased incidence of tumors by chemical induction ( J:98823 )

• following treatment with MNU, mice develop gastric cancer (in 17 of 19 mice) of with 1 is a carcinoma in, 15 are well-differentiated adenocarcinomas, 1 is a moderately differentiated adenocarcinoma and 1 is a lymphoma compared to similarly treated wild type mice that develop gastric carcinoma (in 5 of 9 mice) all of which are well-differentiated adenocarcinomas

• unlike in wild-type mice, treatment with troglitazone does no inhibit MNU-induced carcinogenesis

cardiovascular system

abnormal retina vasculature morphology ( J:116269 )

• following treatment with STZ, mice exhibit a 2.1-fold increase in retinal leukostasis compared to in similarly treated wild-type mice

• following treatment with STZ, retinal leakage is increased 1.9-fold compared to in similarly treated wild-type mice

immune system

leukostasis ( J:116269 )

• following treatment with STZ, mice exhibit a 2.1-fold increase in retinal leukostasis compared to in similarly treated wild-type mice

abnormal bone marrow development ( J:89250 )

• cultured bone marrow cells exhibit reduced adipogenesis but increased osteogenesis compared to wild-type cells

vision/eye

abnormal retina vasculature morphology ( J:116269 )

• following treatment with STZ, mice exhibit a 2.1-fold increase in retinal leukostasis compared to in similarly treated wild-type mice

• following treatment with STZ, retinal leakage is increased 1.9-fold compared to in similarly treated wild-type mice

hematopoietic system

leukostasis ( J:116269 )

• following treatment with STZ, mice exhibit a 2.1-fold increase in retinal leukostasis compared to in similarly treated wild-type mice

Genotype
MGI:3818960

ht11

• Allelic Composition: Pparg^tm1Tka/Pparg⁺
• Genetic Background: involves: C57BL/6 * CBA * ICR

immune system

immune system phenotype ( J:58222 )

N • despite changes in B cell physiology, T cell morphology and physiology are normal

abnormal B cell physiology ( J:58222 )

• B cell viability is greater than for wild-type B cells

increased B cell proliferation ( J:58222 )

• mice exhibit an exaggerated basal proliferation rate and proliferative response to stimulation with LPS of anti-IgM compared to wild-type B cells

• however, increased B cell proliferation can be inhibited by treatment with Pparg agonists

increased IgG level ( J:58222 )

• in an unprimed state

increased IgM level ( J:58222 )

• in an unprimed state

abnormal humoral immune response ( J:58222 )

• mice exhibit enhanced antigen-specific immune response and increased production of antigen specific antibodies compared to wild-type mice

increased interferon-gamma secretion ( J:58222 )

• antigen-stimulated splenocytes produce increased IFN-gamma levels compared to in wild-type cells

increased interleukin-2 secretion ( J:58222 )

• antigen-stimulated splenocytes produce increased IL2 levels compared to in wild-type cells

increased susceptibility to induced arthritis ( J:58222 )

• mice develop more severe antigen-induced arthritis than wild-type mice

homeostasis/metabolism

abnormal response to injury ( J:68579 )

• following intestinal ischemia and reperfusion, mice exhibit greater injury compared to similarly treated wild-type mice

skeleton

increased susceptibility to induced arthritis ( J:58222 )

• mice develop more severe antigen-induced arthritis than wild-type mice

hematopoietic system

abnormal B cell physiology ( J:58222 )

• B cell viability is greater than for wild-type B cells

increased B cell proliferation ( J:58222 )

• mice exhibit an exaggerated basal proliferation rate and proliferative response to stimulation with LPS of anti-IgM compared to wild-type B cells

• however, increased B cell proliferation can be inhibited by treatment with Pparg agonists

increased IgG level ( J:58222 )

• in an unprimed state

increased IgM level ( J:58222 )

• in an unprimed state

cellular

increased B cell proliferation ( J:58222 )

• mice exhibit an exaggerated basal proliferation rate and proliferative response to stimulation with LPS of anti-IgM compared to wild-type B cells

• however, increased B cell proliferation can be inhibited by treatment with Pparg agonists

Genotype
MGI:3575675

ht12

• Allelic Composition: Pparg^tm1Wwah/Pparg⁺
• Genetic Background: Not Specified

immune system

immune system phenotype ( J:71272 )

N • no difference observed in the wound healing process compared to wildtype

Genotype
MGI:5581951

cn13

• Allelic Composition: Ctnnb1^tm2Kem/Ctnnb1^tm2Kem; Pparg^{tm1.1(tTA)Jmgr}/Pparg⁺; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

skeleton

skeleton phenotype ( J:178340 )

N • mice exhibit normal bone formation and osteoblast surface/numbers

decreased osteoclast cell number ( J:178340 )

abnormal osteoclast physiology ( J:178340 )

• decreased proliferation of osteoclast precursors

increased bone volume ( J:178340 )

• at 6 months

increased compact bone volume ( J:178340 )

• at 6 months

abnormal trabecular bone morphology ( J:178340 )

• more trabecular bone and bone surface at 6 months

increased trabecular bone volume ( J:178340 )

• at 6 months

increased bone trabecula number ( J:178340 )

• with reduced spacing at 6 months

increased trabecular bone thickness ( J:178340 )

• at 6 months

osteopetrosis ( J:178340 )

decreased bone resorption ( J:178340 )

hematopoietic system

extramedullary hematopoiesis ( J:178340 )

decreased osteoclast cell number ( J:178340 )

abnormal osteoclast physiology ( J:178340 )

• decreased proliferation of osteoclast precursors

immune system

decreased osteoclast cell number ( J:178340 )

abnormal osteoclast physiology ( J:178340 )

• decreased proliferation of osteoclast precursors

Genotype
MGI:5581952

cn14

• Allelic Composition: Ctnnb1^tm2Kem/Ctnnb1⁺; Pparg^{tm1.1(tTA)Jmgr}/Pparg⁺; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

skeleton

skeleton phenotype ( J:178340 )

N • doxycycline-treated mice exhibit normal numbers of osteoblasts, bone formation and bone mineral apposition rates

increased osteoclast cell number ( J:178340 )

• in doxycycline-treated mice

abnormal osteoclast physiology ( J:178340 )

• doxycycline-treated bone marrow cultures exhibit reduced osteoclast precursor proliferation compared with control cultures

abnormal trabecular bone morphology ( J:178340 )

• decreased bone surface in doxycycline-treated mice

decreased trabecular bone volume ( J:178340 )

• trabecular, cortical and total in doxycycline-treated mice

decreased bone trabecula number ( J:178340 )

• with increased spacing in doxycycline-treated mice

decreased trabecular bone mass ( J:178340 )

• in doxycycline-treated mice

decreased trabecular bone thickness ( J:178340 )

• in doxycycline-treated mice

osteoporosis ( J:178340 )

• in doxycycline-treated mice

increased bone resorption ( J:178340 )

• in doxycycline-treated mice

hematopoietic system

increased osteoclast cell number ( J:178340 )

• in doxycycline-treated mice

abnormal osteoclast physiology ( J:178340 )

• doxycycline-treated bone marrow cultures exhibit reduced osteoclast precursor proliferation compared with control cultures

immune system

increased osteoclast cell number ( J:178340 )

• in doxycycline-treated mice

abnormal osteoclast physiology ( J:178340 )

• doxycycline-treated bone marrow cultures exhibit reduced osteoclast precursor proliferation compared with control cultures

Genotype
MGI:5581950

cn15

• Allelic Composition: Ctnnb1^tm2Kem/Ctnnb1^tm2Kem; Pparg^{tm1.1(tTA)Jmgr}/Pparg⁺; Tg(tetO-cre)1Jaw/0; Tg(tetO-HIST1H2BJ/GFP)47Efu/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1

skeleton

abnormal osteoclast differentiation ( J:178340 )

• cultured bone marrow cells contain fewer osteoclast precursors compared with control mice

hematopoietic system

abnormal osteoclast differentiation ( J:178340 )

• cultured bone marrow cells contain fewer osteoclast precursors compared with control mice

cellular

abnormal osteoclast differentiation ( J:178340 )

• cultured bone marrow cells contain fewer osteoclast precursors compared with control mice

immune system

abnormal osteoclast differentiation ( J:178340 )

• cultured bone marrow cells contain fewer osteoclast precursors compared with control mice

Genotype
MGI:5581956

cn16

• Allelic Composition: Ctnnb1^tm1Mmt/Ctnnb1⁺; Pparg^{tm1.1(tTA)Jmgr}/Pparg⁺; Tg(tetO-cre)1Jaw/0
• Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6

skeleton

skeleton phenotype ( J:178340 )

N • doxycycline-treated mice exhibit normal bone formation and numbers of osteoblasts

abnormal osteoclast differentiation ( J:178340 )

• impaired in doxycycline-treated mice

decreased osteoclast cell number ( J:178340 )

• in doxycycline-treated mice

increased bone volume ( J:178340 )

• as early as P15 in doxycycline-treated mice

• 27-fold from 10 months of age in doxycycline-treated mice

increased compact bone volume ( J:178340 )

• in doxycycline-treated mice

abnormal trabecular bone morphology ( J:178340 )

• 4.6-fold increase in trabecular bone surface and a smaller bone surface to bone volume in doxycycline-treated mice

increased trabecular bone volume ( J:178340 )

• trabecular, cortical and total volume as early as P15 in doxycycline-treated mice

increased bone trabecula number ( J:178340 )

• 3.6-fold with reduced trabecular separation in doxycycline-treated mice

increased trabecular bone thickness ( J:178340 )

• 8.5-fold in doxycycline-treated mice

osteopetrosis ( J:178340 )

• severe in doxycycline-treated mice

• in mice following adult onset activation with doxycycline

decreased bone resorption ( J:178340 )

• in doxycycline-treated mice

hematopoietic system

abnormal osteoclast differentiation ( J:178340 )

• impaired in doxycycline-treated mice

extramedullary hematopoiesis ( J:178340 )

• in doxycycline-treated mice

decreased bone marrow cell number ( J:178340 )

• at 4 months in doxycycline-treated mice

absent bone marrow cell ( J:178340 )

• at 10 months in doxycycline-treated mice

decreased osteoclast cell number ( J:178340 )

• in doxycycline-treated mice

increased splenocyte number ( J:178340 )

• gradual in doxycycline-treated mice

cellular

abnormal osteoclast differentiation ( J:178340 )

• impaired in doxycycline-treated mice

immune system

abnormal osteoclast differentiation ( J:178340 )

• impaired in doxycycline-treated mice

decreased osteoclast cell number ( J:178340 )

• in doxycycline-treated mice

increased splenocyte number ( J:178340 )

• gradual in doxycycline-treated mice

Genotype
MGI:3695904

cx17

• Allelic Composition: Lep^ob/Lep^ob; Pparg^tm1Avp/Pparg⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

homeostasis/metabolism

increased circulating triglyceride level ( J:116568 )

• increased compared to mice that are wild-type at the Lep locus and on a high fat diet

abnormal glucose homeostasis ( J:116568 )

increased circulating glucose level ( J:116568 )

• increased at 4 weeks of age in fed mice relative to Lep^ob homozygotes and wild-type mice

increased circulating insulin level ( J:116568 )

• not significantly different from Lep^ob homozygotes, but increased compared to wild-type mice

insulin resistance ( J:116568 )

• increased relative to Lep^ob homozygotes

decreased circulating adiponectin level ( J:116568 )

• reduced plasma adiponectin levels, independent of presence or absence of the Lep^ob allele

growth/size/body

decreased body fat mass ( J:116568 )

• at 12 weeks of age fat mass is reduced relative to Lep^ob homozygotes

decreased body weight ( J:116568 )

• at 5 weeks of age body mass is decreased relative to Lep^ob homozygotes, but is still higher than in wild-type mice

• at 12 weeks of age body mass is reduced by 14% and 12 % in females and males, respectively, relative to Lep^ob homozygotes

increased liver weight ( J:116568 )

• at 12 weeks of age relative to Lep^ob homozygotes

adipose tissue

abnormal white adipose tissue amount ( J:116568 )

• reduced amount of gonadal and subcutaneous white fat relative to Lep^ob homozygotes

decreased body fat mass ( J:116568 )

• at 12 weeks of age fat mass is reduced relative to Lep^ob homozygotes

decreased fat cell size ( J:116568 )

• smaller adipocytes in the gonadal and subcutaneous white fat relative to Lep^ob homozygotes

abnormal gonadal fat pad morphology ( J:116568 )

• reduced amount relative to Lep^ob homozygotes

liver/biliary system

increased liver weight ( J:116568 )

• at 12 weeks of age relative to Lep^ob homozygotes

hepatic steatosis ( J:116568 )

• at 12 weeks of age relative to Lep^ob homozygotes

muscle

abnormal skeletal muscle morphology ( J:116568 )

• reduced intramyocellular lipid deposition relative to Lep^ob homozygotes

behavior/neurological

polyphagia ( J:116568 )

• not significantly different from Lep^ob homozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial partial lipodystrophy		DOID:0050440	OMIM:PS151660	J:116568

Genotype
MGI:3641270

cx18

• Allelic Composition: Atp2b2^m1Mae/Atp2b2⁺; Pparg^tm2Mae/Pparg⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

hearing/vestibular/ear

impaired hearing ( J:110607 )

• severe hearing loss

behavior/neurological

decreased startle reflex ( J:110607 )

• decreased acoustic startle amplitude but normal movement and motor function

nervous system

abnormal prepulse inhibition ( J:110607 )

• absent