Phenotypes associated with this allele

• Allele Symbol: Pparg^tm1.1Gonz
• Allele Name: targeted mutation 1.1, Frank J Gonzales
• Allele ID: MGI:2384321
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Pparg^tm1.1Gonz/Pparg^tm1.1Gonz	involves: 129X1/SvJ * FVB	MGI:3663798
cn2	Pparg^tm1.1Gonz/Pparg^tm1.1Gonz Tg(Ins2-cre)25Mgn/0	involves: 129 * C57 * FVB	MGI:3045806
cn3	Pparg^tm1.1Gonz/Pparg^tm1.1Gonz Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6	MGI:4939883
cn4	Pparg^tm1.1Gonz/Pparg^tm1.1Gonz Tg(Mx1-cre)1Cgn/?	involves: 129X1/SvJ * C57BL/6 * CBA * FVB/N	MGI:3722298
cn5	Pparg^tm1.1Gonz/Pparg^tm1.1Gonz Tg(Aqp2-cre)1Dek/0	involves: 129X1/SvJ * C57BL/6 * SJL	MGI:5437733

Genotype
MGI:3663798

cn1

• Allelic Composition: Pparg^tm1.1Gonz/Pparg^tm1.1Gonz
• Genetic Background: involves: 129X1/SvJ * FVB

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

cardiovascular system

increased myocardial fiber size ( J:112034 )

• exhibit significantly larger cardiomyocytes at 6 months of age

cardiac hypertrophy ( J:112034 )

• observe age-progressive cardiac hypertrophy, however systolic cardiac function is preserved

• about 10% at 3 months of age and about 22% at 6 months of age show cardiac hypertrophy

• hearts show increased expression of embryonic genes ANP and beta-MHC and elevated NF-kappaB activity

decreased heart rate ( J:112034 )

• significantly lower resting heart rate

muscle

increased myocardial fiber size ( J:112034 )

• exhibit significantly larger cardiomyocytes at 6 months of age

growth/size/body

cardiac hypertrophy ( J:112034 )

• observe age-progressive cardiac hypertrophy, however systolic cardiac function is preserved

• about 10% at 3 months of age and about 22% at 6 months of age show cardiac hypertrophy

• hearts show increased expression of embryonic genes ANP and beta-MHC and elevated NF-kappaB activity

Genotype
MGI:3045806

cn2

• Allelic Composition: Pparg^tm1.1Gonz/Pparg^tm1.1Gonz; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129 * C57 * FVB

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:89959 )

• islets in mutant mice are about twice the size of those in wild-type littermates primarily as a result of beta cell hyperplasia

• however, on a high fat diet a significantly smaller increase in beta cell mass is seen in mutant mice (8.3-fold in wild-type vs. 2.1-fols d in mutant mice) resulting in significantly lower beta cell mass in mutants compared to wild-type littermates

• no other significant differences between mutant and wild-type littermates were found

Genotype
MGI:4939883

cn3

• Allelic Composition: Pparg^tm1.1Gonz/Pparg^tm1.1Gonz; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6

renal/urinary system

increased renal glomerulus apoptosis ( J:168799 )

• increase in the number of apoptotic cells in the glomeruli

increased urine protein level ( J:168799 )

• mutants exhibit excretion of high molecular weight proteins in the urine

albuminuria ( J:168799 )

• mutants exhibit excretion of albumin in the urine

abnormal kidney morphology ( J:168799 )

• females develop severe nephropathy at 4-6 months of age

enlarged kidney ( J:168799 )

• kidney hypertrophy

increased kidney weight ( J:168799 )

• increase in kidney weight due to glomerulomegaly

abnormal nephron morphology ( J:168799 )

• nephrons exhibit coarsening and fusion of podocyte foot processes

abnormal podocyte foot process morphology ( J:168799 )

• cell destruction in the glomeruli is indicated by the accumulation of electrolucent material in podocyte foot processes

fused podocyte foot processes ( J:168799 )

• fusion of podocyte foot processes

increased renal glomerulus basement membrane thickness ( J:168799 )

• glomerular basement membrane thickening

abnormal renal glomerulus morphology ( J:168799 )

• increase in glomerular cell number

increased mesangial cell number ( J:168799 )

• mesangial hypercellularity

glomerulonephritis ( J:168799 )

• severe glomerular inflammation associated with increased renal macrophage infiltration

expanded mesangial matrix ( J:168799 )

• mesangial matrix expansion

renal glomerulus hypertrophy ( J:168799 )

• glomerulomegaly; glomeruli are enlarged in focal regions within the kidneys

homeostasis/metabolism

increased circulating creatine level ( J:168799 )

increased urine protein level ( J:168799 )

• mutants exhibit excretion of high molecular weight proteins in the urine

albuminuria ( J:168799 )

• mutants exhibit excretion of albumin in the urine

immune system

impaired macrophage phagocytosis ( J:168799 )

• peritoneal macrophages exhibit defective phagocytosis resulting in impaired apoptotic cell uptake and an accumulation of apoptotic cells

abnormal peritoneal macrophage morphology ( J:168799 )

• peritoneal macrophages exhibit lower phagosome content and smaller filopodia than control macrophages

increased IgG level ( J:168799 )

• mutants exhibit a marked deposition of IgG in the mesangial matrix

increased IgM level ( J:168799 )

• mutants exhibit a marked deposition of IgM in the mesangial matrix

abnormal macrophage activation involved in immune response ( J:168799 )

• apoptotic cells in mutants cannot reduce proinflammatory response as in controls, indicating enhanced proinflammatory macrophage activation within the kidney glomeruli

increased autoantibody level ( J:168799 )

• mutants develop autoantibodies against nuclear proteins, ssDNA, and dsDNA

increased anti-nuclear antigen antibody level ( J:168799 )

increased anti-double stranded DNA antibody level ( J:168799 )

increased anti-single stranded DNA antibody level ( J:168799 )

glomerulonephritis ( J:168799 )

• severe glomerular inflammation associated with increased renal macrophage infiltration

hematopoietic system

impaired macrophage phagocytosis ( J:168799 )

• peritoneal macrophages exhibit defective phagocytosis resulting in impaired apoptotic cell uptake and an accumulation of apoptotic cells

abnormal peritoneal macrophage morphology ( J:168799 )

• peritoneal macrophages exhibit lower phagosome content and smaller filopodia than control macrophages

increased IgG level ( J:168799 )

• mutants exhibit a marked deposition of IgG in the mesangial matrix

increased IgM level ( J:168799 )

• mutants exhibit a marked deposition of IgM in the mesangial matrix

abnormal macrophage activation involved in immune response ( J:168799 )

• apoptotic cells in mutants cannot reduce proinflammatory response as in controls, indicating enhanced proinflammatory macrophage activation within the kidney glomeruli

cellular

increased mesangial cell number ( J:168799 )

• mesangial hypercellularity

increased renal glomerulus apoptosis ( J:168799 )

• increase in the number of apoptotic cells in the glomeruli

impaired macrophage phagocytosis ( J:168799 )

• peritoneal macrophages exhibit defective phagocytosis resulting in impaired apoptotic cell uptake and an accumulation of apoptotic cells

growth/size/body

enlarged kidney ( J:168799 )

• kidney hypertrophy

increased kidney weight ( J:168799 )

• increase in kidney weight due to glomerulomegaly

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:168799

Genotype
MGI:3722298

cn4

• Allelic Composition: Pparg^tm1.1Gonz/Pparg^tm1.1Gonz; Tg(Mx1-cre)1Cgn/?
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * CBA * FVB/N

immune system

abnormal macrophage physiology ( J:75777 )

• basal cholesterol efflux from cholesterol-loaded macrophages to HDL is reduced

hematopoietic system

abnormal macrophage physiology ( J:75777 )

• basal cholesterol efflux from cholesterol-loaded macrophages to HDL is reduced

Genotype
MGI:5437733

cn5

• Allelic Composition: Pparg^tm1.1Gonz/Pparg^tm1.1Gonz; Tg(Aqp2-cre)1Dek/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * SJL

growth/size/body

abnormal body weight ( J:99873 )

• after a 9-day rosiglitazone (RGZ) treatment, mice fail to exhibit a significant increase in body weight gain as a result of fluid retention, unlike similarly-treated control mice

cardiovascular system

abnormal blood volume ( J:99873 )

• after RGZ treatment, mice exhibit a significantly reduced plasma volume expansion relative to similarly-treated control mice, as shown by the Evans blue technique

hematopoietic system

abnormal hematocrit ( J:99873 )

• after RGZ treatment, mice fail to exhibit a significant fall in hematocrit levels, unlike similarly-treated control mice

homeostasis/metabolism

abnormal circulating aldosterone level ( J:99873 )

• after RGZ treatment, mice fail to exhibit a significant fall in plasma aldosterone levels, unlike similarly-treated control mice

abnormal urine sodium level ( J:99873 )

• after a 9-day RGZ treatment, mice fail to exhibit a significant reduction in urinary Na excretion, unlike similarly-treated control mice where Na excretion is reduced at day 6 and returns to normal at day 8

• after RGZ treatment, mice fail to exhibit induction of a positive Na balance (where intake > excretion), unlike similarly-treated control mice

abnormal physiological response to xenobiotic ( J:99873 )

• mice are resistant to RGZ-induced fluid retention (increase in body weight and plasma volume expansion) seen in control mice

• RGZ-induced changes in sodium transport are significantly blocked in primary cultures of collecting duct (CD) cells

renal/urinary system

abnormal urine sodium level ( J:99873 )

• after a 9-day RGZ treatment, mice fail to exhibit a significant reduction in urinary Na excretion, unlike similarly-treated control mice where Na excretion is reduced at day 6 and returns to normal at day 8

• after RGZ treatment, mice fail to exhibit induction of a positive Na balance (where intake > excretion), unlike similarly-treated control mice

abnormal renal sodium ion transport ( J:99873 )

• after RGZ treatment, primary cultures of mutant collecting duct (CD) cells fail to exhibit a reduction in transepithelial resistance or show an increase in transepithelial ₂₂Na flux in an amiloride-sensitive manner, unlike similarly-treated control CD cells