Phenotypes associated with this allele

• Allele Symbol: Alb^em1(icre)Gpt
• Allele Name: endonuclease-mediated mutation 1, GemPharmatech Co., Ltd
• Allele ID: MGI:7309680
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Alb^em1(icre)Gpt/Alb^+ Cers5^em1Gpt/Cers5^em1Gpt	C57BL/6JGpt-Alb^em1(icre)Gpt Cers5^em1Gpt	MGI:7785006
cn2	Mir32^em1Gpt/Mir32^em1Gpt Alb^em1(icre)Gpt/Alb^+	C57BL/6JGpt-Mir32^em1Gpt Alb^em1(icre)Gpt	MGI:7580538
cn3	Ywhab^em1Gpt/Ywhab^em1Gpt Alb^em1(icre)Gpt/Alb^+	C57BL/6JGpt-Ywhab^em1Gpt Alb^em1(icre)Gpt	MGI:7328453

Genotype
MGI:7785006

cn1

• Allelic Composition: Alb^em1(icre)Gpt/Alb⁺; Cers5^em1Gpt/Cers5^em1Gpt
• Genetic Background: C57BL/6JGpt-Alb^em1(icre)Gpt Cers5^em1Gpt

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

homeostasis/metabolism

abnormal bile salt homeostasis ( J:345383 )

♂ • male mice fed either a standard control (SC) diet or a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 8 weeks show hepatic bile acid (BA) pools that are more conducive to liver fibrosis development, with significantly increased hydrophobic 12alpha-OH BAs [cholic acids (CAs) and deoxycholic acids (DCAs)] and decreased hydrophilic non-12alpha-OH BAs [muricholic acids (MCAs), hyodeoxycholic acids (HDCAs) and ursodeoxycholic acids (UDCAs)]

♂ • UDCA (hydrophilic non-12alpha-OH BA) is significantly decreased by CDAHFD feeding, such that CDAHFD-fed males show a further reduction in UDCA content relative to SC-fed males and CDAHFD-fed wild-type controls

increased susceptibility to injury ( J:345383 )

♂ • male mice fed a CDAHFD for 8 weeks show more severe liver fibrosis, an increased number of hepatic alpha-SMA-positive cells, and higher mRNA expression levels of hepatic fibrosis factors (Acta2, Col1a1, and Tgfb1) than CDAHFD-fed wild-type controls

♂ • however, CDAHFD-fed males show no differences in the severity of liver steatosis and inflammation, as indicated by similar gross liver morphology, liver weight/body weight index, serum transaminase levels, liver histology, and expression of hepatic inflammatory factors relative to CDAHFD-fed controls

liver/biliary system

liver fibrosis ( J:345383 )

♂ • CDAHFD-fed males show more severe liver fibrosis than CDAHFD-fed wild-type controls, as determined by Masson and Sirius red staining

♂ • profibrotic effect might be attributed to inhibition of BA alternative synthesis pathway

abnormal liver physiology ( J:345383 )

♂ • males fed either a SC diet or a CDAHFD show a significant decrease in hepatic mRNA and protein levels of Cyp27a1 (a key enzyme in the alternative pathway of bile acid synthesis) relative to diet-matched controls

Genotype
MGI:7580538

cn2

• Allelic Composition: Mir32^em1Gpt/Mir32^em1Gpt; Alb^em1(icre)Gpt/Alb⁺
• Genetic Background: C57BL/6JGpt-Mir32^em1Gpt Alb^em1(icre)Gpt

liver/biliary system

decreased liver cholesterol level ( J:344660 )

• mice fed a high-fat diet (HFD) for 12 weeks exhibit significantly lower hepatic cholesterol levels than diet-matched control mice

• however, hepatic cholesterol levels are relatively normal under standard-fat diet (SFD) conditions

decreased liver triglyceride level ( J:344660 )

• HFD-fed mice exhibit significantly lower hepatic TG levels than diet-matched control mice

• however, hepatic TG levels are normal under SFD conditions

decreased liver weight ( J:344660 )

• HFD-fed mice exhibit a significantly lower liver weight to body weight ratio (LW/BW) than diet-matched controls

• however, LW/BW ratio is normal under SFD conditions

decreased susceptibility to diet-induced hepatic steatosis ( J:344660 )

• mice fed a HFD for 12 weeks show significantly less hepatic steatosis than diet-matched controls, as determined by liver macroscopic appearance, H&E staining, Oil Red O staining, LW/BW ratio, and hepatic lipid contents

• administration of Ad-shRNA targeting INSIG1 (insulin induced gene 1, a direct target of Mir32) abrogates the alleviation of hepatic steatosis, insulin resistance, hyperlipidemia, and overexpression of lipogenic genes in HFD-fed mice

abnormal liver physiology ( J:344660 )

• HFD-fed mice show activation of AKT signaling in the liver while mRNA and protein levels of hepatic genes involved in fatty acyl-CoA, triglyceride, and cholesterol biosynthesis are markedly reduced

• HFD-fed mice show significantly alleviated hepatic endoplasmic reticulum stress relative to diet-matched control mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:344660 )

N • mice exhibit normal oxygen consumption, carbon dioxide production, respiratory exchange rate (RER), and heat generation regardless of whether they are fed a HFD or SFD

decreased circulating cholesterol level ( J:344660 )

• HFD-fed mice exhibit significantly lower total serum cholesterol levels than diet-matched control mice

decreased circulating LDL cholesterol level ( J:344660 )

• HFD-fed mice exhibit significantly lower serum LDL cholesterol levels than diet-matched control mice

decreased circulating alanine transaminase level ( J:344660 )

• HFD-fed mice exhibit significantly lower serum ALT levels than diet-matched control mice

• however, serum ALT levels are relatively normal under SFD conditions

decreased circulating aspartate transaminase level ( J:344660 )

• HFD-fed mice exhibit significantly lower serum AST levels than diet-matched control mice

• however, serum AST levels are not significantly altered under SFD conditions

improved glucose tolerance ( J:344660 )

• HFD-fed mice show improved glucose tolerance relative to diet-matched control mice, as indicated by an intraperitoneal glucose tolerance test (IPGTT)

increased insulin sensitivity ( J:344660 )

• HFD-fed mice show enhanced insulin sensitivity relative to diet-matched control mice, as indicated by an insulin tolerance test (IPITT

decreased liver cholesterol level ( J:344660 )

• mice fed a high-fat diet (HFD) for 12 weeks exhibit significantly lower hepatic cholesterol levels than diet-matched control mice

• however, hepatic cholesterol levels are relatively normal under standard-fat diet (SFD) conditions

decreased liver triglyceride level ( J:344660 )

• HFD-fed mice exhibit significantly lower hepatic TG levels than diet-matched control mice

• however, hepatic TG levels are normal under SFD conditions

abnormal lipid metabolism ( J:344660 )

• lipidomic analysis of livers from HFD-fed mice showed a significant reduction in triglyceride and cholesterol ester species relative to diet-matched controls; specifically, TG_48:1, TG_48:2, TG_48:3, TG_49:1, TG_50:1, TG_50:2, TG_50:3, TG_52:1, TG_54:2, CE_22:6, and CE_18:2 are dramatically reduced

cellular

decreased endoplasmic reticulum stress ( J:344660 )

• HFD-fed mice show significantly alleviated hepatic endoplasmic reticulum stress relative to diet-matched control mice

growth/size/body

growth/size/body region phenotype ( J:344660 )

N • mice exhibit normal body weight regardless of whether they are fed a HFD or SFD

behavior/neurological

behavior/neurological phenotype ( J:344660 )

N • mice exhibit normal food intake and total activity regardless of whether they are fed a HFD or SFD

Genotype
MGI:7328453

cn3

• Allelic Composition: Ywhab^em1Gpt/Ywhab^em1Gpt; Alb^em1(icre)Gpt/Alb⁺
• Genetic Background: C57BL/6JGpt-Ywhab^em1Gpt Alb^em1(icre)Gpt

homeostasis/metabolism

increased circulating glucose level ( J:323777 )

• after the injection of pyruvate

enhanced gluconeogenesis ( J:323777 )

• in hepatocytes due to a lack of glucagon signaling inhibition

impaired glucose tolerance ( J:323777 )

• in a glucose tolerance test after the injection of pyruvate

decreased liver glycogen level ( J:323777 )

liver/biliary system

decreased liver glycogen level ( J:323777 )