Phenotypes associated with this allele

• Allele Symbol: Ilrun^{tm1a(KOMP)Wtsi}
• Allele Name: targeted mutation 1a, Wellcome Trust Sanger Institute
• Allele ID: MGI:4944352
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ilrun^tm1a(KOMP)Wtsi/Ilrun^tm1a(KOMP)Wtsi	involves: C57BL/6N	MGI:6507954

Genotype
MGI:6507954

hm1

• Allelic Composition: Ilrun^{tm1a(KOMP)Wtsi}/Ilrun^{tm1a(KOMP)Wtsi}
• Genetic Background: involves: C57BL/6N

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

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:302091 )

N • 4-hour fasted plasma triglyceride (TG) and nonesterified fatty acid (NEFA) levels are normal on a chow diet

N • TG levels and distribution are normal over the course of 14 weeks on a Western-type diet (WTD) diet

decreased insulin secretion ( J:302091 )

• both chow-fed and HFD-fed mice exhibit reduced glucose-stimulated insulin secretion

decreased circulating phospholipid level ( J:302091 )

• on a chow diet, 4-hour fasted plasma phospholipid (PL) levels are significantly lower than those in wild-type controls

• plasma PL levels are significantly reduced over the course of 14 weeks on a WTD diet, and at 2 weeks after a high fat diet (HFD)

decreased circulating triglyceride level ( J:302091 )

• WTD-fed, 4-h fasted mice injected with Poloxamer 407 (an inhibitor of lipoprotein lipase activity) show significantly lower plasma TG levels than wild-type controls, resulting in a ~32% reduction in VLDL-TG secretion rate

decreased circulating VLDL triglyceride level ( J:302091 )

• WTD-fed, 4-h fasted mice injected with Poloxamer 407 (an inhibitor of lipoprotein lipase activity) show a ~32% reduction in VLDL-TG secretion rate

• however, secretion of newly synthesized apoB100 and apoB48 in response to LPL inhibition is normal

impaired glucose tolerance ( J:302091 )

• both chow-fed and HFD-fed mice exhibit impaired glucose tolerance

• steady-state glucose, gluconeogenesis and whole-body insulin sensitivity are normal under chow or HFD conditions

• body weight gain and weight of metabolic tissues (liver, white or brown adipose, subcutaneous) is normal under HFD conditions

abnormal cholesterol homeostasis ( J:302091 )

• hepatic apoA-I production and subsequent HDL formation is attenuated resulting in decreased plasma HDL-C levels

• reconstitution in chow-fed liver with human ILRUN restores Apoa1 transcript and protein levels to those seen in wild-type controls

• HDL catabolism and SR-BI (scavenger receptor class B1)-mediated HDL selective uptake are normal

abnormal circulating non-HDL cholesterol level ( J:302091 )

• plasma non-HDL cholesterol levels are significantly reduced over the course of 14 weeks on a WTD diet

decreased circulating cholesterol level ( J:302091 )

• on a chow diet, 4-hour fasted plasma total cholesterol (TC) levels are significantly lower than those in wild-type controls

• plasma TC levels are significantly reduced over the course of 14 weeks on a WTD diet, and at 2 weeks after a high fat diet (HFD)

• fractional cholesterol absorption is normal in chow-fed mice and food intake and fecal neutral sterol excretion are normal in WTD-fed mice

decreased circulating HDL cholesterol level ( J:302091 )

• on a chow diet, 4-hour fasted plasma HDL-C levels are significantly lower than those in wild-type controls

• plasma HDL-C levels and TC in fractions representing large HDL are significantly reduced over the course of 14 weeks on a WTD diet

decreased circulating LDL cholesterol level ( J:302091 )

• TC in fractions representing small LDL particles are significantly reduced over the course of 14 weeks on a WTD diet

decreased liver cholesterol level ( J:302091 )

• 25% lower liver TC levels after 14 weeks of WTD

• however, hepatic TC content is normal in chow-fed mice

decreased liver triglyceride level ( J:302091 )

• 19% lower liver TG levels after 14 weeks of WTD

• however, hepatic TG content is normal in chow-fed mice

abnormal apolipoprotein level ( J:302091 )

• primary hepatocytes show a significant reduction in mRNA and protein expression of apoA-I (a major protein constituent of HDL particles required for HDL formation)

• liver apoA-I protein expression is decreased by ~32% in chow-fed mice, and markedly reduced in WTD-fed mice in line with decreased apoA-I associated with HDL particles of different sizes

abnormal circulating apolipoprotein level ( J:302091 )

• total plasma apoA-I and apoA-I levels in HDL fractions of plasma are reduced in chow-fed mice

abnormal lipid metabolism ( J:302091 )

• significantly reduced expression of Apoa4, a positive regulator of VLDL particle expansion, after 14 weeks of WTD

decreased lipogenesis ( J:302091 )

• modestly reduced expression of lipogenic genes after 14 weeks of WTD

liver/biliary system

decreased liver cholesterol level ( J:302091 )

• 25% lower liver TC levels after 14 weeks of WTD

• however, hepatic TC content is normal in chow-fed mice

decreased liver triglyceride level ( J:302091 )

• 19% lower liver TG levels after 14 weeks of WTD

• however, hepatic TG content is normal in chow-fed mice

decreased liver weight ( J:302091 )

• liver weight to body weight ratio is significantly reduced after 14 weeks on a WTD diet

• however, no difference is noted on a chow diet

abnormal liver physiology ( J:302091 )

• altered hepatic intracellular lipid transport and metabolism, including reduced lipogenesis and VLDL particle expansion, partially contributing to reduced VLDL-TG secretion

• significantly increased PPARalpha protein abundance in liver and primary hepatocytes

growth/size/body

decreased body weight ( J:302091 )

• body weight is significantly reduced after 14 weeks on a WTD diet

• however, no difference is noted on a chow diet

endocrine/exocrine glands

decreased insulin secretion ( J:302091 )

• both chow-fed and HFD-fed mice exhibit reduced glucose-stimulated insulin secretion