Phenotypes associated with this allele

• Allele Symbol: Med19^{tm1c(EUCOMM)Wtsi}
• Allele Name: targeted mutation 1c, Wellcome Trust Sanger Institute
• Allele ID: MGI:6502866
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Med19^tm1c(EUCOMM)Wtsi/Med19^tm1c(EUCOMM)Wtsi Tg(Adipoq-icre/ERT2)1Soff/0	involves: C57BL/6J * C57BL/6N	MGI:6505536
cn2	Med19^tm1c(EUCOMM)Wtsi/Med19^tm1c(EUCOMM)Wtsi Tg(Adipoq-cre)1Evdr/0	involves: C57BL/6J * C57BL/6N * FVB/NJ	MGI:6505535

Genotype
MGI:6505536

cn1

• Allelic Composition: Med19^{tm1c(EUCOMM)Wtsi}/Med19^{tm1c(EUCOMM)Wtsi}; Tg(Adipoq-icre/ERT2)1Soff/0
• Genetic Background: involves: C57BL/6J * C57BL/6N

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

growth/size/body

growth/size/body region phenotype ( J:298822 )

N • mice show no significant change in body weight at 21 days after a 5-day tamoxifen treatment initiated at 12 weeks of age

adipose tissue

whitened brown adipose tissue morphology ( J:298822 )

• brown adipose tissue (BAT) accumulates unilocular lipid droplets, indicating whitening of brown fat

• Oil red O staining confirmed that pockets of white-adipocyte-like cells within BAT are adipocytes

decreased white fat cell number ( J:298822 )

• marked reduction of white adipocytes at 21 days after tamoxifen treatment

abnormal white fat cell size ( J:298822 )

• irregularly sized white adipocytes in residual white fat tissue at 21 days after tamoxifen treatment

decreased gonadal fat pad weight ( J:298822 )

• dramatic reduction in gonadal WAT tissue (gWAT) mass at 21 days after tamoxifen treatment

decreased inguinal fat pad weight ( J:298822 )

• dramatic reduction in inguinal WAT tissue (iWAT) mass at 21 days after tamoxifen treatment

decreased white adipose tissue mass ( J:298822 )

• dramatic reduction in white adipose tissue mass at 21 days after tamoxifen treatment

lipodystrophy ( J:298822 )

• loss of WAT due to increased apoptosis and macrophage infiltration

increased white adipose tissue apoptosis ( J:298822 )

• accumulation of apoptotic cells in iWAT after tamoxifen treatment, as determined by cleaved caspace-3 staining

white adipose tissue inflammation ( J:298822 )

• increased white adipose tissue (WAT) inflammation with significant macrophage infiltration in gWAT and iWAT after tamoxifen treatment

homeostasis/metabolism

impaired lipolysis ( J:298822 )

• surprisingly, lipolytic activity is impaired in inguinal WAT tissue (iWAT) explants, as shown in a lipolysis assay

• mRNA expression of lipolysis genes is reduced in iWAT

immune system

white adipose tissue inflammation ( J:298822 )

• increased white adipose tissue (WAT) inflammation with significant macrophage infiltration in gWAT and iWAT after tamoxifen treatment

cellular

increased white adipose tissue apoptosis ( J:298822 )

• accumulation of apoptotic cells in iWAT after tamoxifen treatment, as determined by cleaved caspace-3 staining

Genotype
MGI:6505535

cn2

• Allelic Composition: Med19^{tm1c(EUCOMM)Wtsi}/Med19^{tm1c(EUCOMM)Wtsi}; Tg(Adipoq-cre)1Evdr/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * FVB/NJ

growth/size/body

decreased body fat mass ( J:298822 )

• reduced fat mass in both sexes at 12 weeks of age, as revealed by body composition analysis (EchoMRI)

increased lean body mass ( J:298822 )

• slightly increased lean mass in both sexes at 12 weeks of age, as revealed by EchoMRI

increased body weight ( J:298822 )

• increased body weight in both sexes at 9 and 12 weeks of age, but not at 3 or 6 weeks of age

• however, food intake is not significantly altered

enlarged liver ( J:298822 )

• enlarged liver at 12 weeks of age

increased liver weight ( J:298822 )

• markedly increased liver weight at 12 weeks of age

adipose tissue

decreased body fat mass ( J:298822 )

• reduced fat mass in both sexes at 12 weeks of age, as revealed by body composition analysis (EchoMRI)

whitened brown adipose tissue morphology ( J:298822 )

• brown adipose tissue (BAT) contains many white-adipocyte-like unilocular cells, indicating whitening of brown fat

• however, no change in brown adipose tissue (BAT) mass at 3 or 12 weeks of age

decreased gonadal fat pad weight ( J:298822 )

• severely reduced gonadal white fat depot (gWAT) weight in males as early as 3 weeks of age

decreased inguinal fat pad weight ( J:298822 )

• severely reduced inguinal white fat depot (iWAT) weight in males as early as 3 weeks of age

decreased mesenteric fat pad weight ( J:298822 )

• reduction in mesenteric WAT (mWAT) weight at 12 weeks of age

decreased retroperitoneal fat pad weight ( J:298822 )

• reduction in retroperitoneal WAT (rWAT) weight at 12 weeks of age

abnormal interscapular fat pad morphology ( J:298822 )

• interscapular BAT is much paler at 12 weeks of age, resembling WAT

abnormal white adipose tissue morphology ( J:298822 )

• small amount of residual WAT appears unhealthy with sparse, irregularly sized adipocytes among a fibrous extracellular matrix

decreased subcutaneous adipose tissue amount ( J:298822 )

• reduction in anterior subcutaneous WAT (asWAT) weight at 12 weeks of age

decreased white fat cell number ( J:298822 )

• sparse white adipocytes

abnormal white fat cell size ( J:298822 )

• irregularly sized white adipocytes

decreased white adipose tissue mass ( J:298822 )

• dramatic reduction in white adipose tissue mass at 12 weeks of age

• however, no change in brown adipose tissue (BAT) mass at 3 or 12 weeks of age

abnormal brown adipose tissue physiology ( J:298822 )

• mRNA expression of BAT genes, including Ucp1, is reduced

abnormal white adipose tissue physiology ( J:298822 )

• gene expression analysis of gWAT and iWAT revealed reduced mRNA levels of the adipocyte genes aP2, C/EBPalpha, and PPARgamma; mRNA expression of C/EBPbeta and KLF5 is either unchanged or elevated

homeostasis/metabolism

hyperglycemia ( J:298822 )

• both sexes are hyperglycemic

increased circulating insulin level ( J:298822 )

• markedly increased fasting serum insulin levels

impaired glucose tolerance ( J:298822 )

• both sexes are glucose intolerant

insulin resistance ( J:298822 )

• impaired response to insulin in insulin tolerance test

increased liver triglyceride level ( J:298822 )

• 4-fold increase in liver triglyceride content

liver/biliary system

enlarged liver ( J:298822 )

• enlarged liver at 12 weeks of age

increased liver weight ( J:298822 )

• markedly increased liver weight at 12 weeks of age

increased liver triglyceride level ( J:298822 )

• 4-fold increase in liver triglyceride content

hepatic steatosis ( J:298822 )

• massive accumulation of lipid droplets in liver at 12 weeks of age

pale liver ( J:298822 )

• pale liver at 12 weeks of age

abnormal liver physiology ( J:298822 )

• impaired hepatic insulin signaling, as assessed by phosphorylation of Akt in response to insulin

integument

decreased subcutaneous adipose tissue amount ( J:298822 )

• reduction in anterior subcutaneous WAT (asWAT) weight at 12 weeks of age