Phenotypes associated with this allele

• Allele Symbol: Gfm1^em1Rmrt
• Allele Name: endonuclease-mediated mutation 1, Ramon Marti
• Allele ID: MGI:7858914
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gfm1^em1Rmrt/Gfm1^em1Rmrt	C57BL/6NTac-Gfm1^em1Rmrt	MGI:8369243
ht2	Gfm1^em1Rmrt/Gfm1^em2Rmrt	involves: C57BL/6J * C57BL/6NTac	MGI:8369247

Genotype
MGI:8369243

hm1

• Allelic Composition: Gfm1^em1Rmrt/Gfm1^em1Rmrt
• Genetic Background: C57BL/6NTac-Gfm1^em1Rmrt

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

mortality/aging

embryonic lethality, complete penetrance ( J:361430 )

• no homozygous newborns are obtained from heterozygous intercrosses; no homozygous embryos are found at E10.5 or E13.5

embryonic lethality between implantation and placentation, complete penetrance ( J:361430 )

• empty implantation sites with no embryonic rests are frequently present in gestating females at E10.5, suggesting post-implantation lethality between E5.5 and E9.5

Genotype
MGI:8369247

ht2

• Allelic Composition: Gfm1^em1Rmrt/Gfm1^em2Rmrt
• Genetic Background: involves: C57BL/6J * C57BL/6NTac

homeostasis/metabolism

decreased mitochondria enzyme/coenzyme activity ( J:361430 )

• mice show a moderate reduction of mitochondrial respiratory complex I enzyme activity in liver and brain homogenates, not observed in Gfm1^em2Rmrt homozygotes

impaired mitochondrial translation ( J:361430 )

• in organello translation assays show a further reduction of mitochondrial translation in liver and brain mitochondria from 8-week-old mice relative to Gfm1^em2Rmrt homozygotes (which show impaired mitochondrial translation in liver, but not in brain)

• mitochondrial translation rates are below 50% of those in wild-type controls in both tissues

decreased protein level ( J:361430 )

• mice show a more severe (~98%) depletion of GFM1/EFG1 protein levels in liver and brain mitochondria than Gfm1^em2Rmrt homozygotes, with steady-state Gfm1 mRNA levels only slightly decreased in liver but normal in brain relative to wild-type levels

• moreover, a strong reduction (~97.5%) of GFM1/EFG1 protein levels is detected in heart

• however, protein levels of other mitochondrial translation elongation factors are normal in liver and brain

increased brain enzyme/coenzyme activity ( J:361430 )

• mice show a slight increase in the activity of citrate synthase (a TCA cycle enzyme) in brain, but NOT in liver and heart, suggesting increased mitochondrial proliferation in this organ

decreased cytochrome-c oxidase activity ( J:361430 )

• mice show a marked reduction of respiratory chain complex IV enzyme activity in liver (~38.4% of wild-type) and brain (~58.1% of wild-type) homogenates

• despite a strong reduction of cardiac GFM1/EFG1 levels, only a moderate reduction of complex IV enzyme activity is detected in heart (~62.8% of wild-type)

cellular

decreased mitochondria enzyme/coenzyme activity ( J:361430 )

• mice show a moderate reduction of mitochondrial respiratory complex I enzyme activity in liver and brain homogenates, not observed in Gfm1^em2Rmrt homozygotes

increased mitochondrial fission ( J:361430 )

• mice show a slight increase in the activity of citrate synthase (a TCA cycle enzyme) in brain, but NOT in liver and heart, suggesting increased mitochondrial proliferation in this organ

impaired mitochondrial translation ( J:361430 )

• in organello translation assays show a further reduction of mitochondrial translation in liver and brain mitochondria from 8-week-old mice relative to Gfm1^em2Rmrt homozygotes (which show impaired mitochondrial translation in liver, but not in brain)

• mitochondrial translation rates are below 50% of those in wild-type controls in both tissues

abnormal oxidative phosphorylation ( J:361430 )

• pulse-chase labeling of mtDNA-encoded proteins shows that the half-life of newly synthetized MT-CO1, the core catalytic subunit of Complex IV, in liver mitochondria is shorter than in wild-type controls (1.39 h versus 2.16 h), indicating instability

• however, the stability of newly synthetized Complex I subunits MT-ND1 and MT-ND2 and Complex III MT-CYTB is not affected

abnormal mitochondrial ATP synthesis coupled electron transport ( J:361430 )

• analysis of OXPHOS subunits levels by BN-PAGE and immunodetection using complex-specific antibodies shows a significant reduction in the relative amount of assembled complex I and complex IV in liver and brain mitochondria

growth/size/body

decreased body weight ( J:361430 )

♀ • starting at P7, female, but not male, mice show a significant reduction in body weight during the preweaning phase

♀ • however, female body weight is normalized by 2 months of age

nervous system

increased brain enzyme/coenzyme activity ( J:361430 )

• mice show a slight increase in the activity of citrate synthase (a TCA cycle enzyme) in brain, but NOT in liver and heart, suggesting increased mitochondrial proliferation in this organ

mortality/aging

mortality/aging ( J:361430 )

N • mice are viable and exhibit a normal lifespan

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
combined oxidative phosphorylation deficiency 1		DOID:0111474	OMIM:609060	J:361430