Phenotypes associated with this allele

• Allele Symbol: Pparg^tm1Tka
• Allele Name: targeted mutation 1, Takashi Kadowaki
• Allele ID: MGI:2429766
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pparg^tm1Tka/Pparg^tm1Tka	involves: C57BL/6 * CBA	MGI:3818948
ht2	Pparg^tm1Tka/Pparg^+	involves: C57BL/6 * CBA	MGI:3818949
ht3	Pparg^tm1Tka/Pparg^+	involves: C57BL/6 * CBA * ICR	MGI:3818960

Genotype
MGI:3818948

hm1

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

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:58222 )

• mice die between E10.5 and E11.5

• in vitro fertilized embryos transplanted in pseudopregnant females survive until E13.5

embryo

embryonic growth retardation ( J:58222 )

abnormal placenta labyrinth morphology ( J:58222 )

• lumps of cells and fibrinoid materials are found within the labyrinth layer unlike in wild-type mice

abnormal placental labyrinth vasculature morphology ( J:58222 )

• embryonic capillaries are poorly developed within the labyrinth layer compared to in wild-type mice

placental labyrinth hypoplasia ( J:58222 )

• at E10.5

cardiovascular system

abnormal placental labyrinth vasculature morphology ( J:58222 )

• embryonic capillaries are poorly developed within the labyrinth layer compared to in wild-type mice

thin myocardium ( J:58222 )

abnormal heart development ( J:58222 )

• at E10.5, no marked trabeculation occurs as in wild-type mice

cellular

abnormal cell differentiation ( J:58222 , J:89250 )

• embryonic fibroblasts fail to differentiate into adipose cells unlike wild-type embryonic fibroblast cells (J:58222)

• treatment with pioglitazone does not rescue differentiation of embryonic fibroblasts into adipocytes unlike in heterozygous cells (J:58222)

• embryonic stem cells fail to differentiate into adipose cells in culture but osteogenesis is enhanced unlike wild-type cells (J:89250)

growth/size/body

embryonic growth retardation ( J:58222 )

muscle

thin myocardium ( J:58222 )

Genotype
MGI:3818949

ht2

• 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

ht3

• 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