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Phenotypes Associated with This Genotype
Genotype
MGI:3629097
Allelic
Composition
Pnpla2tm1Rze/Pnpla2tm1Rze
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pnpla2tm1Rze mutation (1 available); any Pnpla2 mutation (33 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• pronounced cardiac dysfunction results in premature death for male and female homozygotes; the first mice die around 12 weeks of age
• male mice (50% after 16 weeks) die earlier than female (50% after 20 weeks)
• heterozygous mice have normal life spans

growth/size/body
• mutant hearts have a 1.4x heart weight because of the excess triglycerides (193 mg for mutant vs 131 mg wild-type)
• homozygotes display a 2-fold increase in body fat mass
• homozygotes are heavier than wild-type

homeostasis/metabolism
• after 5 hours of cold exposure, mutant body temperature is only 25 degrees C
• when mutants are exposed to cold for 5 hours, they suffer from life-threatening hypothermia as a result of impaired catabolism to triglycerides to brown adipose tissue
• after 18 hours of fasting, body temperature drops to 28.4 degrees C vs 35.4 degrees in wild-type with prolonged fasting
• after a 6-hour fast, mice have significantly lower basal glucose values compared to wild-type
• in the fed state, plasma insulin levels are reduced by 42% in mutants compared to wild-type
• plasma leptin levels are elevated by 2.1-fold in fed mutants and by 4.4-fold in fasted mutant mice
• at death
• oxygen consumption decreases to 25% of that of wild-type after 18 hours of fasting
• RQ in mutants deviates from wild-type during fasting; RQ remains constant whereas in wild-type, it decreases with increasing fasting time
• after a 6-hour fast, null mice show improved glucose tolerance compared to wild-type
• maximal decline of blood glucose levels is more pronounced (34 mg/dl vs 53 mg/dl in wild-type) in Pnpla-deficient mice and persists for the entire 3 hour observation period
• total cholesterol (due to decreased HDL levels ) is reduced by 22%
• in mutants, levels are reduced by 30% in the fed state and by 62% in the fasted state
• levels are decreased by 66%
• reduced VLDL levels are found in mutants
• in non-cardiac tissue the most pronounced accumulation of triglycerides is a >10-fold increase seen in the testis and kidney; smaller (1.5-4-fold) increases are seen in all tissues including the liver
• there is a 20-fold increase in triglyceride content in cardiac muscle by 12 weeks of age in mutants
• in mutants there is decreased lipolytic activities in white (-82%) and brown (-85%) adipose tissues, cardiac muscle (-31%), skeletal muscle (-44%), testis (-69%) and liver (-73%)

adipose tissue
• mutant mice have enlarged lipid droplets (1395 micrometer vs 67 micrometer in wild-type) in brown adipocytes
• mutants have an 8.5 fold increase in wet weight of intracapsular brown adipose tissue
• homozygotes display a 1.6 fold increase in wet weight of gonadal white adipose tissue compared to controls
• homozygotes display a 2.1 fold increase in wet weight of inguinal white adipose tissue compared to controls
• mutants have an 8.5 fold increase in wet weight of intracapsular brown adipose tissue
• mutant mice have enlarged lipid droplets (4690 micrometer vs 3382 micrometer in wild-type) in white adipocytes

cardiovascular system
• congestion is observed in pulmonary vessels at death; not observed in mice before 14 weeks of age
• there is a 20-fold increase in triglyceride content in cardiac muscle by 12 weeks of age in mutants
• in homozygotes there is severe triglyceride accumulation in cardiac muscle; at 12 weeks of age, mutants have a 20-fold higher triglyceride content in myocytes compared to wild-type
• lipid droplets show an age-dependent increase in size and number in cardiomyocytes of mutants beginning with microvesicular droplets at 6 weeks and progressing to large droplets by 18 weeks
• the interventricular septum in mutant hearts is significantly thickened and increases in thickness with age
• mutant hearts have a 1.4x heart weight because of the excess triglycerides (193 mg for mutant vs 131 mg wild-type)
• at death; this is not observed in mice before 14 weeks of age
• at death; this is not observed in mice before 14 weeks of age
• there is a marked change in cardiac texture and increase in fibrosis
• massive lipid buildup causes severe cardiac insufficiency in mutants
• at death, cardiac edema and pleural as well as cardiac effusions are observed; these are not observed in mice before 14 weeks of age
• ejection fraction from left ventricle is drastically reduced compared to wild-type (40.2% vs 80.5% in wild-type)
• in mutants there is a moderate induction of apoptosis
• at death, mutants display typical features of congestive heart failure

muscle
• there is a 20-fold increase in triglyceride content in cardiac muscle by 12 weeks of age in mutants
• in homozygotes there is severe triglyceride accumulation in cardiac muscle; at 12 weeks of age, mutants have a 20-fold higher triglyceride content in myocytes compared to wild-type
• lipid droplets show an age-dependent increase in size and number in cardiomyocytes of mutants beginning with microvesicular droplets at 6 weeks and progressing to large droplets by 18 weeks
• ejection fraction from left ventricle is drastically reduced compared to wild-type (40.2% vs 80.5% in wild-type)
• in mutants there is a moderate induction of apoptosis

liver/biliary system

respiratory system
• congestion is observed in pulmonary vessels at death; not observed in mice before 14 weeks of age

cellular
• in mutants there is a moderate induction of apoptosis


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
03/19/2024
MGI 6.23
The Jackson Laboratory