Phenotypes associated with this allele

• Allele Symbol: Slc25a48^em1(IMPC)J
• Allele Name: endonuclease-mediated mutation 1, Jackson
• Allele ID: MGI:6280027
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slc25a48^em1(IMPC)J/Slc25a48^em1(IMPC)J	involves: C57BL/6J * C57BL/6NJ	MGI:7766927

Genotype
MGI:7766927

hm1

• Allelic Composition: Slc25a48^em1(IMPC)J/Slc25a48^em1(IMPC)J
• Genetic Background: involves: C57BL/6J * C57BL/6NJ

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

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:353858 )

N • on a standard diet, mice show no detectable differences in fasting blood glucose levels relative to control littermates

impaired adaptive thermogenesis ( J:353858 )

• mice show a significantly greater drop in rectal temperature than controls in response to cold exposure (a 30 to 8 degrees Celsius challenge for 8 h), indicating impaired cold tolerance

increased choline level ( J:353858 )

• on a standard diet, serum choline levels are significantly higher than in control mice

abnormal phospholipid level ( J:353858 )

• BAT-derived mitochondria show altered abundance of some phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species relative to control mitochondria

• PE species with very-long-chain polyunsaturated fatty acids on the sn-2 position PE (18:0_22:6 and 18:1_22:6) are increased whereas PC species (16:0_22:4 and 18:2_20:2) are reduced in BAT mitochondria

• in contrast, cardiolipin (a well-known mitochondrial membrane lipid species) is not altered in BAT

abnormal glycerophosphocholine level ( J:353858 )

• BAT-derived mitochondria show reduced abundance of the 16:0_22:4 and 18:2_20:2 phosphatidylcholine (PC) species

increased ceramide level ( J:353858 )

• BAT shows elevated ceramides which are involved in the production of mitochondrial ROS by inhibiting complex III and regulating nicotinamide adenine dinucleotide (NAD) phosphate oxidase

abnormal metabolism ( J:353858 )

• on a standard diet, serum choline levels are significantly increased, whereas serum levels of betaine and dimethylglycine (both of which are choline-derived metabolites) are significantly lower than in control mice

adipose tissue

abnormal brown adipose tissue morphology ( J:353858 )

• at 12 weeks of age, mice fed a standard diet show an enlarged brown adipose tissue (BAT) mitochondrial size with less dense cristae than control BAT mitochondria

• however, gross BAT morphology is normal

abnormal brown adipose tissue thermogenesis ( J:353858 )

• respiration of isolated BAT mitochondria via complex I and II is significantly decreased relative to control littermates, indicating impaired BAT thermogenesis

• no differences in BAT mitochondrial respiration are noted in the presence of guanosine diphosphate (GDP), suggesting attenuation of UCP1-mediated BAT thermogenesis

• however, UCP1 and mitochondrial OXPHOS protein levels in BAT are normal

cellular

abnormal mitochondrial inner membrane morphology ( J:353858 )

abnormal mitochondrial crista morphology ( J:353858 )

• at 12 weeks of age, mice fed a standard diet show a reduction in BAT mitochondrial cristae density relative to control littermates

increased mitochondrial size ( J:353858 )

• at 12 weeks of age, mice fed a standard diet show a significant increase in BAT mitochondrial size relative to control littermates

abnormal mitochondrial ATP synthesis coupled electron transport ( J:353858 )

• isolated BAT mitochondria show impaired complex I and II activities, suggesting a possible electron leak in the mitochondrial membrane

• maximal hydrogen peroxide production (JH2O2) is significantly elevated in isolated BAT mitochondria when thioredoxin reductase is inhibited by auranofin

oxidative stress ( J:353858 )

• BAT-derived mitochondria show increased hexosylceramides (HexlCers) known to be associated with increased lipid peroxidation and ROS accumulation; several HexlCers species contain an oxygen adduct, suggesting increased oxidative stress

• BAT shows elevated ceramides which are involved in the production of mitochondrial ROS by inhibiting complex III and regulating nicotinamide adenine dinucleotide (NAD) phosphate oxidase

• consistent with increased mitochondrial H2O2 production, serum levels of malondialdehyde (MDA), a lipid peroxidation marker, are higher than in control mice

growth/size/body

growth/size/body region phenotype ( J:353858 )

N • both sexes develop normally and show no detectable differences in body mass (g) relative to control littermates