Phenotypes associated with this allele

• Allele Symbol: Pparg^tm2Rev
• Allele Name: targeted mutation 2, Ronald M Evans
• Allele ID: MGI:2651605
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Pparg^tm2Rev/Pparg^tm2Rev Tg(Camk2a-cre)62Jzt/?	B6.Cg-Pparg^tm2Rev Tg(Camk2a-cre)62Jzt	MGI:5444199
cn2	Pparg^tm2Rev/Pparg^tm2Rev Tg(Tek-cre)12Flv/?	B6.Cg-Pparg^tm2Rev Tg(Tek-cre)12Flv	MGI:5444197
cn3	Pparg^tm2Rev/Pparg^tm2Rev Tg(Fabp4-cre)1Rev/0	involves: 129S4/SvJae * C57BL/6	MGI:3033749
cn4	Pparg^tm2Rev/Pparg^tm2Rev Tg(Cd4-cre)1Cwi/?	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5444196
cn5	Pparg^tm2Rev/Pparg^tm2Rev Tg(Tek-cre)1Ywa/?	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:5444193
cn6	Pparg^tm2Rev/Pparg^tm2Rev Tg(Krt1-15-cre/PGR*)22Cot/?	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:5444195
cn7	Pparg^tm2Rev/Pparg^tm2Rev Tg(Lhb-cre)1Sac/?	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:5444194
cn8	Pparg^tm2Rev/Pparg^tm2Rev Tg(Tagln-cre)1Her/?	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:5444198
cn9	Pparg^tm2Rev/Pparg^tm2Rev Tg(Ucp1-cre)1Evdr/0	involves: 129S4/SvJae * FVB	MGI:6361694

Genotype
MGI:5444199

cn1

• Allelic Composition: Pparg^tm2Rev/Pparg^tm2Rev; Tg(Camk2a-cre)62Jzt/?
• Genetic Background: B6.Cg-Pparg^tm2Rev Tg(Camk2a-cre)62Jzt

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

nervous system

nervous system phenotype ( J:148757 )

N • gross brain structures are normal and overall appearance is normal

abnormal neuron physiology ( J:148757 )

• neurons in culture suffer more severe damage from oxygen-glucose deprivation than controls

• more susceptible to H2O2 induced injury than controls

brain ischemia ( J:148757 )

• develop 40% larger infarctions after middle cerebral artery occlusion

• increased neurological dysfunction as well

• mortality not affected

growth/size/body

growth/size/body region phenotype ( J:148757 )

N • growth and body weight are normal

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:148757 )

N • normal body temperature

behavior/neurological

behavior/neurological phenotype ( J:148757 )

N • activity is normal

Genotype
MGI:5444197

cn2

• Allelic Composition: Pparg^tm2Rev/Pparg^tm2Rev; Tg(Tek-cre)12Flv/?
• Genetic Background: B6.Cg-Pparg^tm2Rev Tg(Tek-cre)12Flv

growth/size/body

decreased body weight ( J:154216 )

• about 5% less than controls

enlarged spleen ( J:154216 )

immune system

enlarged spleen ( J:154216 )

hematopoietic system

enlarged spleen ( J:154216 )

decreased hematocrit ( J:154216 )

• slightly reduced hematocrit

cardiovascular system

increased mean systemic arterial blood pressure ( J:154216 )

• higher baseline pressure

• greater increase when challenged with angiotensin II

abnormal vascular endothelial cell physiology ( J:154216 )

• reduced NO production in blood vessel endothelium

abnormal vasodilation ( J:154216 )

• impaired endothelium dependent acetylcholine mediated relaxation of aortic rings

muscle

abnormal vasodilation ( J:154216 )

• impaired endothelium dependent acetylcholine mediated relaxation of aortic rings

impaired muscle relaxation ( J:154216 )

• impaired endothelium dependent acetylcholine mediated relaxation of aortic rings

Genotype
MGI:3033749

cn3

• Allelic Composition: Pparg^tm2Rev/Pparg^tm2Rev; Tg(Fabp4-cre)1Rev/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6

adipose tissue

abnormal white adipose tissue amount ( J:88210 )

• cell loss greater than 80%

abnormal brown adipose tissue morphology ( J:88210 )

• vacuole form sometimes like white adipose cells rather than typical brown fat cells

decreased brown adipose tissue amount ( J:88210 )

• brown adipose tissue mass reduced more than 70% by 6 months of age

decreased brown fat cell number ( J:88210 )

• cell numbers reduced more than 95%

abnormal brown fat cell size ( J:88210 )

increased brown fat cell size ( J:88210 )

• cells are larger and variable in size

increased white fat cell size ( J:88210 )

• more than 50% of white adipocytes are highly hypertrophic

decreased interscapular fat pad weight ( J:88210 )

• diminution of interscapular fat pads detectable by 4-6 weeks

growth/size/body

slow postnatal weight gain ( J:88210 )

• weight gain on a high fat diet is decreased

enlarged liver ( J:88210 )

• hepatomegaly eventually develops as well

homeostasis/metabolism

increased circulating insulin level ( J:88210 )

• insulin levels are increased

insulin resistance ( J:88210 )

• insulin became less efficient at suppressing glucose production

liver/biliary system

enlarged liver ( J:88210 )

• hepatomegaly eventually develops as well

hepatic steatosis ( J:88210 )

• livers were beginning to be steatotic at 6 months of age

Genotype
MGI:5444196

cn4

• Allelic Composition: Pparg^tm2Rev/Pparg^tm2Rev; Tg(Cd4-cre)1Cwi/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

immune system

abnormal T-helper 17 cell differentiation ( J:153358 )

• increased

• accumulate in the CNS rather than the spleen in experimental autoimmune encephalitis

increased susceptibility to experimental autoimmune encephalomyelitis ( J:153358 )

• earlier onset and aggravated disease course during the T-cell dependent phase

• difference from controls disappears after 15 days

• increased number of CD4+ T cells at the beginning of clinical disease (day 8) and at the disease peak (day 13) but not at day 18

• three fold increase in myelin oligodendrocyte glycoprotein specific T cells at disease peak

hematopoietic system

abnormal T-helper 17 cell differentiation ( J:153358 )

• increased

• accumulate in the CNS rather than the spleen in experimental autoimmune encephalitis

Genotype
MGI:5444193

cn5

• Allelic Composition: Pparg^tm2Rev/Pparg^tm2Rev; Tg(Tek-cre)1Ywa/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

growth/size/body

heart right ventricle hypertrophy ( J:155909 )

• increased in normal air but similar to controls when both are under hypoxia

postnatal growth retardation ( J:123403 )

• low body weight at weaning strictly dependent on maternal genotype

• body weight is normal in the first post natal week

• weight gain ceases completely at 10 days of age and does not resume until after weaning

enlarged spleen ( J:130475 )

• spleen to body weight ratio increases 1.4-2 fold in adults and in 5 and 18 day old pups

integument

skin inflammation ( J:123403 )

• leukocyte infiltration around follicles between 20 and 32 days

• macrophage accumulate in the skin starting at 10 days

abnormal skin adnexa morphology ( J:123403 )

abnormal mammary gland alveolus morphology ( J:123403 )

• fewer lobular alveolar structures in female mammary glands at day 4 of lactation

• more and larger adipocytes in female mammary glands at day 4 of lactation

premature hair loss ( J:123403 )

• near complete hair loss on the trunk strictly dependent on maternal genotype

• fostering on wild-type mothers corrects hair loss

• hair loss begins around 16 days of age and is complete on the trunk at about 18 days

• new hair growth begins 2-3 weeks after weaning and coat remains normal thereafter

abnormal hair follicle morphology ( J:123403 )

• formation of follicular cysts leading to shaft ejection at 20 days

abnormal hair cycle ( J:123403 )

abnormal hair cycle anagen phase ( J:123403 )

• new anagen phase does not begin until around 32 days

abnormal hair shedding ( J:123403 )

• formation of follicular cysts leading to shaft ejection at 20 days

liver/biliary system

pale liver ( J:123403 )

• pale liver with increased lipid accumulation

cardiovascular system

abnormal pulmonary artery morphology ( J:155909 )

• increased number of muscularized distal pulmonary arteries

heart right ventricle hypertrophy ( J:155909 )

• increased in normal air but similar to controls when both are under hypoxia

increased right ventricle systolic pressure ( J:155909 )

• increased in normal air but similar to controls when both are under hypoxia

• less complete recovery from hypoxia than controls 4 weeks after return to normal air

homeostasis/metabolism

increased triglyceride level ( J:155909 )

• higher triglyceride levels

• higher triglyceride/HDL

skeleton

abnormal bone structure ( J:130475 )

• irregular, uneven bone structure

abnormal osteoclast morphology ( J:130475 )

abnormal osteoclast differentiation ( J:160910 )

• fail to produce osteoclasts in response to rosiglitazone treatment

• no increase in osteoclast numbers

decreased osteoclast cell number ( J:130475 )

• fewer osteoclasts in femur sections while osteoblast numbers are unchanged

abnormal bone marrow cavity morphology ( J:130475 )

• decreased medullary cavity space

increased bone mineral density ( J:130475 )

• 30-70% increase

increased bone volume ( J:130475 )

• bone volume/tissue volume ratio is 40-70% higher than controls in both the proximal and distal regions of the femur and tibia

• increased bone volume

abnormal trabecular bone morphology ( J:130475 )

increased trabecular bone volume ( J:130475 )

abnormal bone trabecula morphology ( J:130475 , J:160910 )

• decreased trabecular separation (J:130475)

• no loss of trabecular bone after rosiglitazone treatment as occurs in controls (J:160910)

increased bone trabecula number ( J:130475 )

increased trabecular bone thickness ( J:130475 )

hematopoietic system

hematopoietic system phenotype ( J:130475 )

N • white blood cell, red blood cell, and platelet counts remain normal

extramedullary hematopoiesis ( J:130475 )

abnormal bone marrow cell morphology/development ( J:130475 )

decreased bone marrow cell number ( J:130475 )

• 35% decrease in cellularity

• both erythroid and granulocytic/monocytic

• hematopoietic stem cells reduced 56%

abnormal osteoclast morphology ( J:130475 )

abnormal osteoclast differentiation ( J:160910 )

• fail to produce osteoclasts in response to rosiglitazone treatment

• no increase in osteoclast numbers

decreased osteoclast cell number ( J:130475 )

• fewer osteoclasts in femur sections while osteoblast numbers are unchanged

abnormal spleen morphology ( J:130475 )

enlarged spleen ( J:130475 )

• spleen to body weight ratio increases 1.4-2 fold in adults and in 5 and 18 day old pups

abnormal splenocyte morphology ( J:130475 )

• accumulation of megakaryocytes in the spleen

increased splenocyte number ( J:130475 )

• 63% increase in spleen cellularity

• both erythroid and granulocytic/monocytic

• hematopoietic stem cells increased 275%

immune system

abnormal osteoclast morphology ( J:130475 )

abnormal osteoclast differentiation ( J:160910 )

• fail to produce osteoclasts in response to rosiglitazone treatment

• no increase in osteoclast numbers

decreased osteoclast cell number ( J:130475 )

• fewer osteoclasts in femur sections while osteoblast numbers are unchanged

abnormal spleen morphology ( J:130475 )

enlarged spleen ( J:130475 )

• spleen to body weight ratio increases 1.4-2 fold in adults and in 5 and 18 day old pups

abnormal splenocyte morphology ( J:130475 )

• accumulation of megakaryocytes in the spleen

increased splenocyte number ( J:130475 )

• 63% increase in spleen cellularity

• both erythroid and granulocytic/monocytic

• hematopoietic stem cells increased 275%

skin inflammation ( J:123403 )

• leukocyte infiltration around follicles between 20 and 32 days

• macrophage accumulate in the skin starting at 10 days

cellular

abnormal osteoclast differentiation ( J:160910 )

• fail to produce osteoclasts in response to rosiglitazone treatment

• no increase in osteoclast numbers

endocrine/exocrine glands

abnormal mammary gland alveolus morphology ( J:123403 )

• fewer lobular alveolar structures in female mammary glands at day 4 of lactation

• more and larger adipocytes in female mammary glands at day 4 of lactation

muscle

heart right ventricle hypertrophy ( J:155909 )

• increased in normal air but similar to controls when both are under hypoxia

Genotype
MGI:5444195

cn6

• Allelic Composition: Pparg^tm2Rev/Pparg^tm2Rev; Tg(Krt1-15-cre/PGR*)22Cot/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

integument

skin inflammation ( J:150977 )

• increased interstitial inflammation

abnormal skin adnexa morphology ( J:150977 )

sebaceous gland atrophy ( J:150977 )

abnormal coat appearance ( J:150977 )

progressive hair loss ( J:150977 )

• starting around 3 months and associated with increased hair loss

matted coat ( J:150977 )

• remaining hair becomes matted

abnormal hair follicle morphology ( J:150977 )

• dystrophic hair follicles

• strands of fibrous connective tissue run perpendicular to the epidermis from dystrophic hair follicles

abnormal hair follicle ostium morphology ( J:150977 )

• follicular ostia are dilated and plugged

abnormal skin morphology ( J:150977 )

abnormal skin sebaceous gland morphology ( J:150977 )

• sometimes dystrophic and contiguous with follicular plugs

hyperkeratosis ( J:150977 )

abnormal skin appearance ( J:150977 )

flaky skin ( J:150977 )

• becomes flaky and crusty

reddish skin ( J:150977 )

• mild

skin fibrosis ( J:150977 )

• perifollicular fibrosis

behavior/neurological

excessive scratching ( J:150977 )

• associated with progressive hair loss

immune system

skin inflammation ( J:150977 )

• increased interstitial inflammation

endocrine/exocrine glands

abnormal skin sebaceous gland morphology ( J:150977 )

• sometimes dystrophic and contiguous with follicular plugs

sebaceous gland atrophy ( J:150977 )

Genotype
MGI:5444194

cn7

• Allelic Composition: Pparg^tm2Rev/Pparg^tm2Rev; Tg(Lhb-cre)1Sac/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

reproductive system

reproductive system phenotype ( J:170272 )

N • both males and females are fertile and produce litters at a normal rate

N • estrus patterns are normal

abnormal diestrus ( J:170272 )

♀ • diestrus levels of LH are elevated 3-fold

decreased litter size ( J:170272 )

homeostasis/metabolism

decreased circulating follicle stimulating hormone level ( J:170272 )

♂ • plasma levels are slightly but significantly reduced in males whereas levels are normal in females

increased luteinizing hormone level ( J:170272 )

♀ • diestrus levels are elevated 3-fold in females whereas male levels are normal

Genotype
MGI:5444198

cn8

• Allelic Composition: Pparg^tm2Rev/Pparg^tm2Rev; Tg(Tagln-cre)1Her/?
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

cardiovascular system

abnormal pulmonary artery morphology ( J:136168 )

• increased muscularization of pulmonary arteries at the alveolar wall

heart right ventricle hypertrophy ( J:136168 )

increased right ventricle systolic pressure ( J:136168 )

• elevated right ventricular systolic pressure

growth/size/body

heart right ventricle hypertrophy ( J:136168 )

muscle

heart right ventricle hypertrophy ( J:136168 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
primary pulmonary hypertension		DOID:14557	OMIM:178600 OMIM:265400 OMIM:615342 OMIM:615343 OMIM:615344	J:136168

Genotype
MGI:6361694

cn9

• Allelic Composition: Pparg^tm2Rev/Pparg^tm2Rev; Tg(Ucp1-cre)1Evdr/0
• Genetic Background: involves: 129S4/SvJae * FVB

adipose tissue

abnormal interscapular fat pad morphology ( J:278806 )

• composed of unilocular adipocytes and fibrotic tissues unlike in controls

homeostasis/metabolism

abnormal amino acid metabolism ( J:278806 )

• following cold exposure, mice fail to exhibit a decrease in branched-chains amino acid plasma concentration unlike in control mice