Phenotypes Associated with This Genotype

Genotype
MGI:3784503

• Allelic Composition: Pparg^tm2(tTA)Yba/Pparg⁺
• Genetic Background: involves: 129S1/SvImJ * C57BL/6

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

Lipodystrophy phenotypes of Pparg^tm2(tTA)Yba/Pparg⁺ mice

reproductive system

reduced fertility ( J:125992 )

• Background Sensitivity: mice exhibit poor fecundity after introgression onto a C57BL/6 background

adipose tissue

adipose tissue phenotype ( J:125992 )

N • despite the development of dyslipidemia and severe insulin resistance, mice do not develop steatosis or type 2 diabetes

abnormal brown adipose tissue morphology ( J:125992 )

• mice exhibit hypertrophy and unilocular lipid deposition in mutant brown adipocytes

• however, defects can be prevented by midgestational administration of doxycycline and reverted by a 6 week treatment with doxycycline

increased brown fat cell size ( J:125992 )

• mice exhibit hypertrophy in mutant brown adipocytes

• however, defects can be prevented by midgestational administration of doxycycline and reverted by a 6 week treatment with doxycycline

decreased gonadal fat pad weight ( J:125992 )

• gonadal fat pads are severely reduced compared to in wild-type mice

• however, defects can be prevented by midgestational administration of doxycycline and reverted by a 6 week treatment with doxycycline

increased interscapular fat pad weight ( J:125992 )

• mice exhibit 'buffalo humps' comprised of swollen interscapular fat pads due to hypertrophy and unilocular lipid deposition in mutant brown adipocytes

• however, defects can be prevented by midgestational administration of doxycycline and reverted by a 6 week treatment with doxycycline

abnormal white adipose tissue morphology ( J:125992 )

• fibrotic white adipose tissue stroma is filled with fragmented lipid droplets and leukocytes

• remaining adipocytes have irregular shapes and range in size from overtly hypertrophic to minuscule cells

• however, defects were prevented by midgestational administration of doxycycline but adipocyte size does not revert following treatment with doxycycline

absent subcutaneous adipose tissue ( J:125992 )

• mice lack subcutaneous adipocytes

abnormal white fat cell morphology ( J:125992 )

• remaining adipocytes have irregular shapes

abnormal white fat cell size ( J:125992 )

• remaining adipocytes range in size from overtly hypertrophic to minuscule cells

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:125992 )

N • despite the development of dyslipidemia and severe insulin resistance, mice do not develop steatosis or type 2 diabetes

hyperglycemia ( J:125992 )

• hyperglycemia develops prepuberty then normalizes latter in life with only sporadic and transient hyperglycemia

• however, treatment with doxycycline reverses metabolic anomalies

increased circulating insulin level ( J:125992 )

• mice exhibit an increase in serum insulin

• however, treatment with doxycycline reverses metabolic anomalies

increased circulating cholesterol level ( J:125992 )

• mice exhibit an increase in serum cholesterol with early onset

• however, treatment with doxycycline reverses metabolic anomalies

increased circulating free fatty acids level ( J:125992 )

• mice exhibit an increase in serum free fatty acids with early onset

• however, treatment with doxycycline reverses metabolic anomalies

increased circulating triglyceride level ( J:125992 )

• mice exhibit an increase in serum triglycerides with early onset

• however, treatment with doxycycline reverses metabolic anomalies

impaired glucose tolerance ( J:125992 )

• mice exhibit severe glucose intolerance

• however, treatment with doxycycline reverses metabolic anomalies

insulin resistance ( J:125992 )

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:125992 )

• mice exhibit pancreas islet cell hyperplasia

• however, treatment with doxycycline reverses metabolic anomalies

pancreas hyperplasia ( J:125992 )

• mice as old as 12 to 18 months exhibit hyperplasia with intact and insulin-laden pancreatic islets with hyperinsulinemia and normoglycemia

liver/biliary system

enlarged liver ( J:125992 )

• liver size is increased by 60% to 150% and is accompanied by hepatocyte hypertrophy and vacuolization

• however, lipid droplet accumulation is not observed

abnormal hepatocyte morphology ( J:125992 )

• mice exhibit hepatocyte hypertrophy and vacuolization

integument

absent subcutaneous adipose tissue ( J:125992 )

• mice lack subcutaneous adipocytes

growth/size/body

pancreas hyperplasia ( J:125992 )

• mice as old as 12 to 18 months exhibit hyperplasia with intact and insulin-laden pancreatic islets with hyperinsulinemia and normoglycemia

enlarged liver ( J:125992 )

• liver size is increased by 60% to 150% and is accompanied by hepatocyte hypertrophy and vacuolization

• however, lipid droplet accumulation is not observed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital generalized lipodystrophy type 2		DOID:0111136	OMIM:269700	J:125992
familial partial lipodystrophy		DOID:0050440	OMIM:PS151660	J:125992