Phenotypes associated with this allele

• Allele Symbol: Slc22a1^tm1Kmgi
• Allele Name: targeted mutation 1, Kathleen M Giacomini
• Allele ID: MGI:5636771
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slc22a1^tm1Kmgi/Slc22a1^tm1Kmgi	involves: 129P2/OlaHsd * C57BL/6J * FVB/N	MGI:5790644

Genotype
MGI:5790644

hm1

• Allelic Composition: Slc22a1^tm1Kmgi/Slc22a1^tm1Kmgi
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * FVB/N

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

homeostasis/metabolism

abnormal fasting circulating glucose level ( J:122106 )

• after 5 days of i.p. metformin treatment (50 mg/kg each day), mutant mice fed a high-fat diet for 8 weeks fail to show any significant changes in 18-hour fasting plasma glucose levels, unlike similarly treated wild-type controls where fasting plasma glucose levels are reduced by >30%

abnormal hepatic glucose production ( J:122106 )

• in culture, metformin (1 mM) fails to significantly lower glucagon-stimulated glucose production in primary mouse hepatocytes, unlike in wild-type hepatocytes where glucose production is reduced by 30%

abnormal physiological response to xenobiotic ( J:122106 )

• metformin's therapeutic effect of lowering fasting plasma glucose levels is completely abolished in mutant mice fed a high-fat diet, unlike in similarly treated wild-type controls

abnormal xenobiotic pharmacokinetics ( J:122106 )

• in culture, primary mouse hepatocytes show a 3.4-fold decrease in metformin uptake and significantly less metformin-stimulated phosphorylation of both AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC, an AMPK target) than wild-type hepatocytes

• at 1 hour after a single oral dose (15 mg/kg) of metformin, mutant mice show normal plasma metformin levels but significantly (4.2-fold) less hepatic metformin accumulation than age-matched wild-type controls

• following a daily i.p. dose of metformin (50 mg/kg) for 3 days, mutant mice show significantly less hepatic phosphorylation of AMPK and ACC than age-matched wild-type controls