Phenotypes associated with this allele

• Allele Symbol: Cyth3^{tm2a(KOMP)Wtsi}
• Allele Name: targeted mutation 2a, Wellcome Trust Sanger Institute
• Allele ID: MGI:4365249
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cyth3^tm2a(KOMP)Wtsi/Cyth3^tm2a(KOMP)Wtsi	C57BL/6N-Cyth3^tm2a(KOMP)Wtsi	MGI:6362991

Genotype
MGI:6362991

hm1

• Allelic Composition: Cyth3^{tm2a(KOMP)Wtsi}/Cyth3^{tm2a(KOMP)Wtsi}
• Genetic Background: C57BL/6N-Cyth3^{tm2a(KOMP)Wtsi}
• Cell Lines: EPD0064_1_E05

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

growth/size/body

growth/size/body region phenotype ( J:272118 )

N • on a chow diet, young adult (7-12 weeks old) male and female show normal total body weight and organ weights relative to wild-type controls

increased lean body mass ( J:272118 )

• aged mice are generally leaner than wild-type mice

decreased susceptibility to weight gain ( J:272118 )

• at >21 weeks of age, body weight of males is significantly lower than that in wild-type controls

• however, body weight is not due to reduced body size, as determined by tibia length of young adult mice

decreased susceptibility to age related obesity ( J:272118 )

• chow-fed males show a reduction in age-induced weight gain with no significant changes in inguinal or gonadal WAT mass (WATi + 6% and WATg +19%) relative to wild-type controls (WATi + 28% and WATg +102%) at 2 years of age

decreased susceptibility to diet-induced obesity ( J:272118 )

• following a high-fat diet (HFD, 60 kJ% fat) for 6 weeks, young adult males show a significantly lower body weight gain and fat mass than HFD-fed wild-type controls; however, lean mass is unaffected

liver/biliary system

decreased liver glycogen level ( J:272118 )

• at 2 years of age, liver glycogen levels of males are 50% lower than those in age-matched wild-type controls

• on a normal-fat control diet (CD, 13 kJ% fa), liver glycogen levels of males are significantly lower than those in CD-fed wild-type controls

• following a HFD for 6 weeks, young adult males fail to show a significant reduction of the already low liver glycogen levels, unlike HFD-fed wild-type controls

decreased liver triglyceride level ( J:272118 )

• following a HFD for 6 weeks, young adult males fail to show an increase in liver lipid content and liver triglyceride levels are significantly lower than those in HFD-fed wild-type controls

abnormal liver physiology ( J:272118 )

• after i.p. insulin injection of chow-fed young adult mice, livers show a significantly lower activation of the insulin receptor (IR)-downstream targets AKT and ERK1/2 relative to wild-type controls; however, phosphorylation of IRbeta is normal

• glucokinase (Gck) expression is significantly reduced in livers from mice fed ad libitum as well as in livers from mice re-fed following a starvation period

• Pepck gene expression is not significantly induced in livers following starvation due to an already high expression of Pepck with food ad libitum; furthermore, repression by re-feeding is significantly lower than that in wild-type controls

adipose tissue

decreased gonadal fat pad weight ( J:272118 )

• at 2 years of age, mice show a significantly smaller increase in gonadal WAT mass (WATg +19%) relative to wild-type controls (WATg +102%)

• following a HFD for 6 weeks, young adult males show a significantly lower gonadal fat pad weight than HFD-fed wild-type controls

decreased inguinal fat pad weight ( J:272118 )

• at 2 years of age, mice show a significantly smaller increase in inguinal WAT mass (WATi + 6%) relative to wild-type controls (WATi + 28%)

• following a HFD for 6 weeks, young adult males show a significantly lower inguinal fat pad weight than HFD-fed wild-type controls

abnormal white adipose tissue physiology ( J:272118 )

• after i.p. insulin injection of chow-fed young adult mice, subcutaneous inguinal white adipose tissue (WATi) shows a 40-50% reduction in AKT and ERK1/2 activation relative to wild-type controls

• at 2 years of age, expression of Pnpla2 (an insulin dependent triglyceride lipase in adipose tissue), is significantly increased in gonadal WAT (WATg), indicating reduced insulin sensitivity

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:272118 )

N • on a chow diet, young adult (7-12 weeks old) male and female mice show no overt signs of diabetes, with no differences in non-fasted blood glucose levels, serum levels of insulin, glucagon, triglycerides, leptin and liver glycogen relative to wild-type controls

N • despite reduced IR-signaling in liver and adipose tissue, young adult mice are both glucose tolerant and insulin tolerant with no significant differences in serum levels of insulin and glucagon following starvation or re-feeding relative to wild-type controls

N • aged (2-yr-old) mice show normal serum levels of insulin, glucagon, triglycerides, and leptin relative to wild-type controls

N • following a HFD for 6 weeks, young adult males show a normal metabolic rate, with no significant changes in oxygen consumption, CO₂ production, energy expenditure or body temperature relative to HFD-fed wild-type controls

abnormal feces lipid level ( J:272118 )

• HFD-fed and aged mice show significantly increased lipid secretion induced by decreased bile acid synthesis

decreased susceptibility to diet-induced obesity ( J:272118 )

• following a high-fat diet (HFD, 60 kJ% fat) for 6 weeks, young adult males show a significantly lower body weight gain and fat mass than HFD-fed wild-type controls; however, lean mass is unaffected

decreased circulating glucose level ( J:272118 )

• at 2 years of age, blood glucose levels of males are significantly lower than those in wild-type controls

• on a CD and HDF diet, blood glucose levels of males are 11% (CD) and 13% (HFD) lower than those in wild-type controls

decreased circulating triglyceride level ( J:272118 )

• after 4 hrs of re-feeding, young adult mice show significantly lower serum triglyceride levels than re-fed wild-type controls

decreased liver glycogen level ( J:272118 )

• at 2 years of age, liver glycogen levels of males are 50% lower than those in age-matched wild-type controls

• on a normal-fat control diet (CD, 13 kJ% fa), liver glycogen levels of males are significantly lower than those in CD-fed wild-type controls

• following a HFD for 6 weeks, young adult males fail to show a significant reduction of the already low liver glycogen levels, unlike HFD-fed wild-type controls

insulin resistance ( J:272118 )

• following a HFD for 6 weeks, young adult males develop insulin resistance but are significantly lighter than HFD-fed wild-type controls

• on a CD diet, glucose clearance is significantly reduced 10 min after insulin administration compared to CD-fed wild-type controls

abnormal bile salt homeostasis ( J:272118 )

• HFD-fed and aged males show a significantly lower expression of bile acid synthetic enzymes (Cyp8b1 and Cyp27a1) relative to wild-type controls

decreased liver triglyceride level ( J:272118 )

• following a HFD for 6 weeks, young adult males fail to show an increase in liver lipid content and liver triglyceride levels are significantly lower than those in HFD-fed wild-type controls

decreased lipogenesis ( J:272118 )

• neither Glut4 nor Fasn (genes coding for de novo lipogenesis) are significantly up-regulated in WATi of young adult mice after re-feeding, unlike in wild-type controls; Srebp1c expression in WATi is by trend lower than that in wild-type controls after re-feeding

digestive/alimentary system

abnormal feces lipid level ( J:272118 )

• HFD-fed and aged mice show significantly increased lipid secretion induced by decreased bile acid synthesis

behavior/neurological

behavior/neurological phenotype ( J:272118 )

N • mice fed a CD or a HFD diet show normal food intake and locomotor activity in metabolic cages relative to similarly fed wild-type controls