Phenotypes Associated with This Genotype

Genotype
MGI:3838352

• Allelic Composition: Agpat2^tm1Garg/Agpat2^tm1Garg
• Genetic Background: involves: 129S6/SvEvTac

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

mortality/aging

decreased survivor rate ( J:146649 )

• only 20% of mice survive past 3 weeks of age

postnatal lethality, incomplete penetrance ( J:146649 )

• 80% of mice die by 3 weeks of age with the majority of these mice dieing within the first week of life

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:231617 )

N • mice exhibit normal plasma triglyceride, cholesterol levels, creatine kinase and creatinine level, and consumption of oxygen and carbon dioxide

decreased circulating leptin level ( J:146649 )

• near absent

decreased body temperature ( J:146649 )

abnormal gas homeostasis ( J:146649 )

increased carbon dioxide production ( J:146649 )

• mice emit 22% more carbon dioxide than wild-type mice

increased oxygen consumption ( J:146649 )

• 24% more than wild-type mice

decreased respiratory quotient ( J:146649 )

• the respiratory exchange ratio is reduced, particularly during the dark phase, compared to in wild-type mice

abnormal glucose homeostasis ( J:146649 )

increased circulating glucose level ( J:231617 )

♀ • in female, but not male, mice

hyperglycemia ( J:146649 )

• as early as day 1 after birth

increased circulating insulin level ( J:146649 , J:231617 )

• during an oral glucose tolerance test whether fasted or not (J:231617)

improved glucose tolerance ( J:231617 )

♂ • male, but not female, mice exhibit increased glucose clearance compared with wild-type mice

insulin resistance ( J:146649 , J:231617 )

• hyperinsulinic-insulin resistant whether fasted or not (J:231617)

• however, mice exhibit normal glucose tolerance and normal insulin sensitivity in a meal tolerance test (J:231617)

abnormal lipid homeostasis ( J:146649 )

increased circulating cholesterol level ( J:231617 )

♀ • in female, but not male, mice

increased circulating triglyceride level ( J:146649 )

• in males but not females

abnormal fatty acids level ( J:146649 )

• fatty acid synthesis is increased compared to in wild-type mice

decreased circulating free fatty acids level ( J:146649 )

• when fed a low fat diet, mice exhibit decreased serum fatty acid levels compared to similarly treated wild-type mice and mice fed a regular diet

• when fed a standard diet, female mice exhibit decreased serum fatty acid levels compared to in wild-type mice

abnormal phospholipid level ( J:146649 )

• male mice exhibit an increase in liver phosphatidyl ethanolamine (PE), phosphatidyl choline (PC), and phosphatidyl serine (PS) levels compared to in wild-type mice

• levels of diacylglyceride are decreased in male mice compared to in wild-type mice

• however, female mice exhibit normal liver phospholipids levels

increased liver triglyceride level ( J:146649 , J:231617 )

• triglyceride levels are increased 6.4-fold in males compared to in wild-type mice (J:146649)

• triglyceride levels are increased 2.1-fold in females compared to in wild-type mice (J:146649)

• however, liver triglyceride levels are decreased in low fat diet fed male mice (by 56%) and female mice compared to in mice fed a regular diet (J:146649)

• triglyceride synthesis in hepatocytes is increased compared to in wild-type cells (J:146649)

• in female and male mice (J:231617)

adipose tissue

decreased brown adipose tissue amount ( J:146649 )

• completely absent

absent subcutaneous adipose tissue ( J:146649 )

decreased white adipose tissue amount ( J:146649 )

• completely absent

decreased total body fat amount ( J:146649 )

• white and brown adipose are completely absent

abnormal abdominal fat pad morphology ( J:146649 )

• absent

decreased percent body fat/body weight ( J:146649 )

• 2% compared to 24% to 29% in wild-type mice

behavior/neurological

increased fluid intake ( J:146649 )

• 3.7 times more than wild-type mice

polydipsia ( J:231617 )

• in male and female mice

increased food intake ( J:146649 , J:231617 )

• mice intake 85% more energy than wild-type mice (J:146649)

♀ • in female, but not male, mice (J:231617)

decreased locomotor activity ( J:146649 )

• particularly during the dark phase

liver/biliary system

increased liver weight ( J:146649 , J:231617 )

• livers are twice as heavy as in wild-type mice at 8 to 10 weeks of age (J:146649)

• however, liver weights are decreased in low fat diet fed male (by 28%) and female mice compared to mice fed a standard diet (J:146649)

• in female and male mice at 16 weeks (J:231617)

increased liver triglyceride level ( J:146649 , J:231617 )

• triglyceride levels are increased 6.4-fold in males compared to in wild-type mice (J:146649)

• triglyceride levels are increased 2.1-fold in females compared to in wild-type mice (J:146649)

• however, liver triglyceride levels are decreased in low fat diet fed male mice (by 56%) and female mice compared to in mice fed a regular diet (J:146649)

• triglyceride synthesis in hepatocytes is increased compared to in wild-type cells (J:146649)

• in female and male mice (J:231617)

hepatic steatosis ( J:146649 )

endocrine/exocrine glands

increased pancreatic beta cell mass ( J:146649 )

enlarged pancreatic islets ( J:146649 )

renal/urinary system

increased kidney weight ( J:146649 )

• at 8 to 10 weeks of age

hematopoietic system

increased spleen weight ( J:146649 )

• at 8 to 10 weeks of age

digestive/alimentary system

abnormal small intestine morphology ( J:146649 )

• elongated at 8 to 10 weeks of age

immune system

increased spleen weight ( J:146649 )

• at 8 to 10 weeks of age

integument

absent subcutaneous adipose tissue ( J:146649 )

growth/size/body

decreased body weight ( J:231617 )

• in female and male mice

increased kidney weight ( J:146649 )

• at 8 to 10 weeks of age

increased liver weight ( J:146649 , J:231617 )

• livers are twice as heavy as in wild-type mice at 8 to 10 weeks of age (J:146649)

• however, liver weights are decreased in low fat diet fed male (by 28%) and female mice compared to mice fed a standard diet (J:146649)

• in female and male mice at 16 weeks (J:231617)

increased spleen weight ( J:146649 )

• at 8 to 10 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital generalized lipodystrophy type 1		DOID:0111135	OMIM:608594	J:146649