Phenotypes Associated with This Genotype

Genotype
MGI:3629413

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

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

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 mitochondrial 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

increased susceptibility to type IV hypersensitivity reaction ( J:258438 )

• in a model of 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis, DNFB-sensitized and challenged mice show a significant increase in ear edema (thickness) 24 h post-challenge relative to DNFB-treated wild-type controls

• topical application of ARN077 (3%), an N-acylethanolamine acid amidase (NAAA) inhibitor, fails to suppress the DNFB-induced ear edema, unlike in similarly treated wild-type controls

muscle

abnormal myocardial fiber mitochondrial 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

abnormal myocardial fiber mitochondrial morphology ( J:63801 )

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

decreased fatty acid oxidation ( J:176083 )

• impaired