Mouse Genome Informatics
ht
    Ppargtm2Yba/Pparg+
involves: 129S1/SvImJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Lipodystrophy phenotypes of Ppargtm2Yba/Pparg+ mice

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

adipose tissue
N
• despite the development of dyslipidemia and severe insulin resistance, mice do not develop steatosis or type 2 diabetes (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
• 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
• 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
• 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
• 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
• mice lack subcutaneous adipocytes
• remaining adipocytes have irregular shapes
• remaining adipocytes range in size from overtly hypertrophic to minuscule cells

homeostasis/metabolism
N
• despite the development of dyslipidemia and severe insulin resistance, mice do not develop steatosis or type 2 diabetes (J:125992)
• hyperglycemia develops prepuberty then normalizes latter in life with only sporadic and transient hyperglycemia
• however, treatment with doxycycline reverses metabolic anomalies
• mice exhibit an increase in serum insulin
• however, treatment with doxycycline reverses metabolic anomalies
• mice exhibit an increase in serum cholesterol with early onset
• however, treatment with doxycycline reverses metabolic anomalies
• mice exhibit an increase in serum free fatty acids with early onset
• however, treatment with doxycycline reverses metabolic anomalies
• mice exhibit an increase in serum triglycerides with early onset
• however, treatment with doxycycline reverses metabolic anomalies
• mice exhibit severe glucose intolerance
• however, treatment with doxycycline reverses metabolic anomalies

endocrine/exocrine glands
• mice exhibit pancreas islet cell hyperplasia
• however, treatment with doxycycline reverses metabolic anomalies
• mice as old as 12 to 18 months exhibit hyperplasia with intact and insulin-laden pancreatic islets with hyperinsulinemia and normoglycemia

liver/biliary system
• mice exhibit hepatocyte hypertrophy and vacuolization
• liver size is increased by 60% to 150% and is accompanied by hepatocyte hypertrophy and vacuolization
• however, lipid droplet accumulation is not observed

integument
• mice lack subcutaneous adipocytes

Mouse Models of Human Disease
OMIM IDRef(s)
Lipodystrophy, Congenital Generalized, Type 2; CGL2 269700 J:125992
Lipodystrophy, Familial Partial, Type 3; FPLD3 604367 J:125992