Phenotypes associated with this allele

• Allele Symbol: Ppara^tm1Gonz
• Allele Name: targeted mutation 1, Frank J Gonzalez
• Allele ID: MGI:1857774
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ppara^tm1Gonz/Ppara^tm1Gonz	129S4/SvJae-Ppara^tm1Gonz	MGI:3037495
hm2	Ppara^tm1Gonz/Ppara^tm1Gonz	B6.129S4-Ppara^tm1Gonz	MGI:3037502
hm3	Ppara^tm1Gonz/Ppara^tm1Gonz	involves: 129S4/SvJae	MGI:3629413
hm4	Ppara^tm1Gonz/Ppara^tm1Gonz	involves: 129S4/SvJae * C57BL/6	MGI:6273162
hm5	Ppara^tm1Gonz/Ppara^tm1Gonz	involves: 129S4/SvJae * C57BL/6J	MGI:4429479
hm6	Ppara^tm1Gonz/Ppara^tm1Gonz	involves: 129S4/SvJae * C57BL/6N	MGI:3037489
hm7	Ppara^tm1Gonz/Ppara^tm1Gonz	involves: C57BL/6	MGI:3037531
cx8	Pkd1^tm1.1Pcha/Pkd1^tm1.1Pcha Ppara^tm1Gonz/Ppara^tm1Gonz	involves: 129 * 129S4/SvJae * C57BL/6	MGI:6317342
cx9	Ldlr^tm1Her/Ldlr^tm1Her Ppara^tm1Gonz/Ppara^tm1Gonz	involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6	MGI:4367223
cx10	Ppara^tm1Gonz/Ppara^tm1Gonz Tg(Ckm-Ppard)LEDpk/0	involves: 129S4/SvJae * C57BL/6 * C57BL/6J * CBA	MGI:4429480

Genotype
MGI:3037495

hm1

• Allelic Composition: Ppara^tm1Gonz/Ppara^tm1Gonz
• Genetic Background: 129S4/SvJae-Ppara^tm1Gonz

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

Accumulation of intracellular lipid in the liver of fasted Ppara^tm1Gonz/Ppara^tm1Gonz mice

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:56056 )

• 2 males out of 32 (male and female) mutants did not survive a 48 hour fast

adipose tissue

increased gonadal fat pad weight ( J:72185 )

• gonadal adipose stores are significantly larger in both female and male mutants

growth/size/body

increased body weight ( J:72185 )

• body weight is significantly elevated in male mutants on a 129S4/SvJae background compared to wild-type

enlarged liver ( J:56056 )

• after a 48 hour fast livers in mutant mice are slightly enlarged and appear pale

homeostasis/metabolism

abnormal circulating ketone body level ( J:56056 )

• fasting did not increase plasma ketone levels despite development of hypoglycemia

abnormal circulating HDL cholesterol level ( J:72185 )

• serum concentrations of HDL cholesterol are significantly higher in 9 month-old mutants on a 129S4/SvJae background compared to wild-type

increased circulating cholesterol level ( J:72185 )

• serum concentrations of cholesterol are significantly higher in 9 month-old mutants on a 129S4/SvJae background compared to wild-type

increased circulating free fatty acids level ( J:56056 )

• after fasting mutants exhibit abnormally high levels of circulating free fatty acids

abnormal glucose homeostasis ( J:56056 )

• in fasted mutants the initial drop in mean blood glucose levels is significantly greater than in fasted wild-types

abnormal circulating glucose level ( J:72932 )

• mutants do not respond to high fat diet with an increase in plasma glucose

abnormal circulating insulin level ( J:72932 )

• mutants do not respond to high fat diet with an increase in insulin levels

insulin resistance ( J:72932 )

• mutants on a 129S4/SvJae background fed a high fat diet do not develop insulin resistance

liver/biliary system

enlarged liver ( J:56056 )

• after a 48 hour fast livers in mutant mice are slightly enlarged and appear pale

hepatic steatosis ( J:56056 , J:72185 )

• lipid accumulation in the hepatocytes of fasted mutants is massive and homogeneous rather than exhibiting a regional pattern as in wild-types (J:56056)

• the majority of the lipid accumulation is in the triglyceride fraction (J:56056)

• in 6 month old mutants hepatic accumulation of lipids is increased (J:72185)

cardiovascular system

abnormal myocardium layer morphology ( J:56056 )

• patchy regions of neutral lipid accumulation are found in the myocardium after fasting

muscle

abnormal myocardium layer morphology ( J:56056 )

• patchy regions of neutral lipid accumulation are found in the myocardium after fasting

Genotype
MGI:3037502

hm2

• Allelic Composition: Ppara^tm1Gonz/Ppara^tm1Gonz
• Genetic Background: B6.129S4-Ppara^tm1Gonz

adipose tissue

increased gonadal fat pad weight ( J:72185 )

• gonadal adipose stores are significantly larger in both female and male mutants

homeostasis/metabolism

abnormal circulating glucose level ( J:72932 )

• mutants do not respond to high fat diet with an increase in plasma glucose

abnormal circulating insulin level ( J:72932 )

• mutants do not respond to high fat diet with an increase in insulin levels

increased circulating triglyceride level ( J:72185 )

• serum concentrations of triglycerides are significantly higher in 9 month-old mutants on a C57BL/6N background

liver/biliary system

hepatic steatosis ( J:72185 )

• in 6 month old mutants hepatic accumulation of lipids is increased

Genotype
MGI:3629413

hm3

• Allelic Composition: Ppara^tm1Gonz/Ppara^tm1Gonz
• Genetic Background: involves: 129S4/SvJae

Ppara^tm1Gonz/Ppara^tm1Gonz mice exhibit myocardial fibrosis and degeneration with age

cardiovascular system

abnormal vascular endothelial cell morphology ( J:63801 )

• number of caveolae in the cardiac capillary endothelium is increased

abnormal myocardial fiber morphology ( J:63801 )

• cristae of mitochondria increase in number and density in myocardial cells at 16 and 32 weeks of age

myocardial fiber degeneration ( J:63801 )

• hearts at 16 weeks of age show myocardial degeneration associated with contraction band necrosis

myocardium necrosis ( J:63801 )

• exhibit contraction band necrosis

cardiac fibrosis ( J:63801 )

• hearts at 16 weeks of age show a little focal fibrosis and by 32 weeks of age, see diffuse fibrosis occupying 1/3 of the inner wall of the myocardium

abnormal cardiovascular system physiology ( J:63801 )

• starvation stress and starvation plus high temperature stress significantly decrease the ATP concentration and increase the calcium concentration in hearts of mutants but not controls

abnormal myocardial fiber physiology ( J:63801 )

• the capacity for constitutive myocardial beta-oxidation of the medium and long chain fatty acids, octanoic acid and palmitic acid, is reduced compared to wild-type, indicating impaired mitochondrial fatty acid catabolism

decreased systemic arterial systolic blood pressure ( J:63801 )

• seen at 16 and 32 weeks of age

hypotension ( J:63801 )

• seen in older mutants

cardiomyopathy ( J:63801 )

• exhibit age-dependent cardiac damage

heart inflammation ( J:63801 )

• inflammatory infiltrates are predominantly composed of macrophages with few lymphocytes and neutrophils

immune system

heart inflammation ( J:63801 )

• inflammatory infiltrates are predominantly composed of macrophages with few lymphocytes and neutrophils

muscle

abnormal myocardial fiber morphology ( J:63801 )

• cristae of mitochondria increase in number and density in myocardial cells at 16 and 32 weeks of age

myocardial fiber degeneration ( J:63801 )

• hearts at 16 weeks of age show myocardial degeneration associated with contraction band necrosis

myocardium necrosis ( J:63801 )

• exhibit contraction band necrosis

cardiomyopathy ( J:63801 )

• exhibit age-dependent cardiac damage

homeostasis/metabolism

decreased fatty acid oxidation ( J:176083 )

• impaired

impaired adaptive thermogenesis ( J:176083 )

decreased circulating glucose level ( J:127793 )

• there is a 25% reduction in fasting glucose levels

increased circulating insulin level ( J:127793 )

• fasting insulin leves tended to be higher regardless of diet

increased circulating cholesterol level ( J:127793 )

• over 60% increase in serum cholesterol levels

increased circulating free fatty acids level ( J:127793 )

• 50% increase in nonesterifed fatty acids in serum of mice fed a zero fat diet

integument

integument phenotype ( J:109090 )

N • no epidermal phenotype is apparent; epidermal layer and surface lipid distribution appear normal

cellular

decreased fatty acid oxidation ( J:176083 )

• impaired

Genotype
MGI:6273162

hm4

• Allelic Composition: Ppara^tm1Gonz/Ppara^tm1Gonz
• Genetic Background: involves: 129S4/SvJae * C57BL/6

renal/urinary system

renal/urinary system phenotype ( J:244067 )

N • mice exhibit normal kidney histology

Genotype
MGI:4429479

hm5

• Allelic Composition: Ppara^tm1Gonz/Ppara^tm1Gonz
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:129848 )

• when fed a high fat diet

abnormal glucose homeostasis ( J:129848 )

• in a hyperinsulinemic-euglycemic clamp study, peripheral glucose disposal in mice fed a high fat diet is improved compared to in similarly treated wild-type mice

improved glucose tolerance ( J:129848 )

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

increased insulin sensitivity ( J:129848 )

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

increased skeletal muscle triglyceride level ( J:129848 )

• in the gastrocnemius when fed a high fat diet

muscle

increased muscle cell glucose uptake ( J:129848 )

• when fed a high fat diet, muscle glucose uptake is improved compared with similarly treated wild-type mice

increased skeletal muscle triglyceride level ( J:129848 )

• in the gastrocnemius when fed a high fat diet

growth/size/body

increased susceptibility to diet-induced obesity ( J:129848 )

• when fed a high fat diet

cellular

increased muscle cell glucose uptake ( J:129848 )

• when fed a high fat diet, muscle glucose uptake is improved compared with similarly treated wild-type mice

Genotype
MGI:3037489

hm6

• Allelic Composition: Ppara^tm1Gonz/Ppara^tm1Gonz
• Genetic Background: involves: 129S4/SvJae * C57BL/6N

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:50024 )

• inhibition of mitochondrial long chain fatty acid transport results the death of all male mutants but only 25% (2/8) of female mutants, no wild-types died as a result of this treatment

• intraperitoneal injection of 100ul of a 50% dextrose solution rescues these mice

• estradiol pretreatment rescues these male mice

cardiovascular system

abnormal myocardial fiber morphology ( J:50024 )

cardiomyopathy ( J:81834 )

• the cardiomyopathic effects (increase in biventricular weight to body weight ratio, increase in left ventricular mass index, hypertrophy) of diabetes are not seen in insulin deficient mutants

homeostasis/metabolism

hypoglycemia ( J:50024 )

• male null mice develop severe hypoglycemia in response to CPT I inhibition

• estradiol rescues male null mice from the CPT I-induced death and impairment in lipid and glucose homeostasis

decreased liver glycogen level ( J:50024 )

• in male mutants compared to female mutants inhibition of mitochondrial long chain fatty acid transport produces a marked decrease in hepatic glycogen levels

delayed wound healing ( J:71272 )

• wound healing is delayed during the first 4 days post wounding

• recruitment of neutrophils and monocytes is impaired in mutants on day 1 post wounding

liver/biliary system

enlarged liver ( J:25516 )

• homozygotes do not develop liver enlargement following treatment with peroxisome proliferators

decreased liver glycogen level ( J:50024 )

• in male mutants compared to female mutants inhibition of mitochondrial long chain fatty acid transport produces a marked decrease in hepatic glycogen levels

abnormal hepatocyte morphology ( J:25516 )

• the number of liver peroxisomes does not increase after treatment with peroxisome proliferators

hepatic steatosis ( J:25516 , J:50024 )

• lipid droplets accumulate in livers of mutant mice treated with peroxisome proliferators (J:25516)

• inhibition of mitochondrial long chain fatty acid transport resulted in fatty degeneration of the liver (J:50024)

• in male mutants almost all the accumulated lipid is triglyceride (J:50024)

muscle

abnormal myocardial fiber morphology ( J:50024 )

cardiomyopathy ( J:81834 )

• the cardiomyopathic effects (increase in biventricular weight to body weight ratio, increase in left ventricular mass index, hypertrophy) of diabetes are not seen in insulin deficient mutants

integument

abnormal epidermal layer morphology ( J:81021 )

abnormal epidermis stratum corneum morphology ( J:81021 )

• between E18.5 and birth mutants display a delay in cornified layer development with a significant reduction in the number of cell layers

• processing of lamellar bilayers at the level of the first extracellular space above the stratum granulosum- cornified layer interface is delayed at E18.5

• no defect in lamellar bilayers is seen in adults

growth/size/body

enlarged liver ( J:25516 )

• homozygotes do not develop liver enlargement following treatment with peroxisome proliferators

Genotype
MGI:3037531

hm7

• Allelic Composition: Ppara^tm1Gonz/Ppara^tm1Gonz
• Genetic Background: involves: C57BL/6

integument

abnormal epidermal layer morphology ( J:64345 )

abnormal keratinocyte differentiation ( J:64345 )

• foci of keratinocytes with nuclei are found in the stratum corneum

• mutants do not respond to peroxisome proliferators with thinning of the epidermis

decreased keratohyalin granule number ( J:64345 )

• fewer keratohylin granules within the granular cells

thin epidermis stratum granulosum ( J:64345 )

• the granular layer is thinner

cellular

abnormal keratinocyte differentiation ( J:64345 )

• foci of keratinocytes with nuclei are found in the stratum corneum

• mutants do not respond to peroxisome proliferators with thinning of the epidermis

Genotype
MGI:6317342

cx8

• Allelic Composition: Pkd1^tm1.1Pcha/Pkd1^tm1.1Pcha; Ppara^tm1Gonz/Ppara^tm1Gonz
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6

renal/urinary system

increased kidney cell proliferation ( J:244067 )

• cyst epithelial proliferation is increased

polycystic kidney ( J:244067 )

• all mice exhibit numerous kidney cysts

enlarged kidney ( J:244067 )

• kidney-weight to body-weight ratio is increased

cellular

increased kidney cell proliferation ( J:244067 )

• cyst epithelial proliferation is increased

growth/size/body

polycystic kidney ( J:244067 )

• all mice exhibit numerous kidney cysts

enlarged kidney ( J:244067 )

• kidney-weight to body-weight ratio is increased

Genotype
MGI:4367223

cx9

• Allelic Composition: Ldlr^tm1Her/Ldlr^tm1Her; Ppara^tm1Gonz/Ppara^tm1Gonz
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:84844 )

N • fasting glucose levels and insulin levels are not increased after dexamethasone treatment

growth/size/body

decreased lean body mass ( J:84844 )

adipose tissue

increased total body fat amount ( J:84844 )

• after dexamethasone treatment

Genotype
MGI:4429480

cx10

• Allelic Composition: Ppara^tm1Gonz/Ppara^tm1Gonz; Tg(Ckm-Ppard)LEDpk/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6J * CBA

homeostasis/metabolism

abnormal glucose tolerance ( J:129848 )

• when fed a high fat diet, mice exhibit greater glucose excursion compared with similarly treated Ppara^tm1Gonz homozygotes but improved glucose tolerance compared with similarly treated wild-type mice