All Phenotypes Aifm1<tm2Pngr> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Aifm1^tm2Pngr/Y Foxg1^tm1(cre)Skm/Foxg1⁺	involves: 129P2/OlaHsd	MGI:3687280
cn2	Apaf1^{Gt(IRESBetageo)XIX18Pgr}/Apaf1^{Gt(IRESBetageo)XIX18Pgr} Aifm1^tm2Pngr/Y Foxg1^tm1(cre)Skm/Foxg1⁺	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:3687281
cn3	Aifm1^tm2Pngr/Y Tg(Ckmm-cre)5Khn/0	involves: 129P2/OlaHsd * FVB	MGI:3687267
cn4	Aifm1^tm2Pngr/Y Tmem163^{Tg(ACTB-cre)2Mrt}/0	involves: 129P2/OlaHsd * FVB/N	MGI:3687265
cn5	Aifm1^tm2Pngr/Aifm1⁺ Tmem163^{Tg(ACTB-cre)2Mrt}/0	involves: 129P2/OlaHsd * FVB/N	MGI:3687266

Allelic Composition	Aifm1^tm2Pngr/Y Foxg1^tm1(cre)Skm/Foxg1⁺
Genetic Background	involves: 129P2/OlaHsd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aifm1^tm2Pngr mutation (0 available); any Aifm1 mutation (11 available)
Foxg1^tm1(cre)Skm mutation (2 available); any Foxg1 mutation (29 available)

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

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:112874 )

• conditional mutants (males) die by E17

cellular

abnormal mitochondrial morphology ( J:112874 )

• mitochondria in cultured neurites are short and fragmented

• while morphology is restored by expression of anchored Pdcd8, mitochondrial length is increased compared to controls; cristae in mutant neurons are dilated and disorganized vs wild-type; cross-sectional distance of mitochondrial cristae is ~2.5-fold wider than wild-type; expression of anchored Pdcd8 reduces intercristae distance from 20 to 17 microns

decreased neuron apoptosis ( J:112874 )

• cultured neurons transfected with a mitochondrially-anchored Pdcd8 show similar survival to wild-type neurons expressing GFP

• after camptothecin treatment, neurons show increased survival vs wild-type over the first 12 hours (~45% loss vs ~55% in wild-type)

increased neuron apoptosis ( J:112874 )

• there is a marked increase in cell death in postmitotic cell regions

abnormal mitochondrial physiology ( J:112874 )

• membrane potential is hyperpolarized relative to wild-type cells

• membrane potential hyperpolarization is restored to normal by expression of anchored Pdcd8

• ATP production and oxygen consumption in cultured mutant neurons is restored by mitochondrially anchored Pdcd8

decreased mitochondrial fission ( J:112874 )

• mutant neurites have few mitochondria vs wild-type

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:112874 )

• expression of complex I respiratory chain complex is abrogated in mutants

nervous system

decreased neuron apoptosis ( J:112874 )

• cultured neurons transfected with a mitochondrially-anchored Pdcd8 show similar survival to wild-type neurons expressing GFP

• after camptothecin treatment, neurons show increased survival vs wild-type over the first 12 hours (~45% loss vs ~55% in wild-type)

increased neuron apoptosis ( J:112874 )

• there is a marked increase in cell death in postmitotic cell regions

thin cerebral cortex ( J:112874 )

• cortical thickness is reduced, mostly at the cortical plate (CP) and intermediate zone (IZ) and to lesser extent the subventricular zone (SVZ)

Allelic Composition	Apaf1^{Gt(IRESBetageo)XIX18Pgr}/Apaf1^{Gt(IRESBetageo)XIX18Pgr} Aifm1^tm2Pngr/Y Foxg1^tm1(cre)Skm/Foxg1⁺
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aifm1^tm2Pngr mutation (0 available); any Aifm1 mutation (11 available)
Apaf1^{Gt(IRESBetageo)XIX18Pgr} mutation (1 available); any Apaf1 mutation (78 available)
Foxg1^tm1(cre)Skm mutation (2 available); any Foxg1 mutation (29 available)

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

cellular

decreased neuron apoptosis ( J:112874 )

• neurons show increased survival vs wild-type after camptothecin treatment

• neurons cultured in pyruvate supplemented media show increased survival after camptothecin treatment

• expression of anchored Pdcd8 does not provide further protection from death to neurons

increased neuron apoptosis ( J:112874 )

• cultured neurons show increased apoptosis reconstituted with wild-type Pdcd8 compared to control; mutant neurons expressing Pdcd8 with a nuclear exclusion sequence show cell death equivalent to control neurons expressing GFP

abnormal mitochondrial physiology ( J:112874 )

• cultured neurons can maintain oxygen consumption after camptothecin treatment if anchored Pdcd8 is expressed

nervous system

decreased neuron apoptosis ( J:112874 )

• neurons show increased survival vs wild-type after camptothecin treatment

• neurons cultured in pyruvate supplemented media show increased survival after camptothecin treatment

• expression of anchored Pdcd8 does not provide further protection from death to neurons

increased neuron apoptosis ( J:112874 )

thickened cerebral cortex ( J:112874 )

• cortex is thickened compared to Pdcd8 conditional embryos

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

growth/size/body

enlarged heart ( J:113016 )

• mice have grossly enlarged hearts at 9 weeks of age

cardiac hypertrophy ( J:113016 )

• 9-week old mice show significant increase in heart weight/tibial-length ratios

weight loss ( J:113016 )

• male mutants appear normal at 2 months; at 3 months, they display significant weight loss

cellular

abnormal mitochondrial morphology ( J:113016 )

• mitochondria display abnormal morphology at 9 weeks but not at 4 weeks of age

abnormal mitochondrial crista morphology ( J:113016 )

• mitochondria display marked cristolysis at 9 weeks but not at 4 weeks of age

increased mitochondrial number ( J:113016 )

• heart muscle has increased number of mitochondria

abnormal aerobic respiration ( J:113016 )

• lipid peroxidation markers are increased >2.5 fold in 9-week old mutants indicating impaired mitochondrial respiration

abnormal mitochondrial physiology ( J:113016 )

• a significant increase in lactate/pyruvate ratio is observed

abnormal respiratory electron transport chain ( J:113016 )

• complex I respiratory chain complex is reduced to ~50% of control levels in heart and gastrocnemius at 5 weeks of age, while complex III level is ~90% of control in heart and gastrocnemius

abnormal mitochondrial ATP synthesis coupled electron transport ( J:113016 )

• respiratory chain enzyme activities in soleus, gastrocnemium and heart muscle is severely reduced; complex I activity in skeletal muscle and heart is reduced (up to 80%) while complex IV activity in the heart is more mildly reduced at 18 weeks of age

oxidative stress ( J:113016 )

• lipid peroxidation markers (indicators or oxidative stress) are increased >2.5 fold in 9-week old mutants

cardiovascular system

abnormal myocardial fiber morphology ( J:113016 )

• heart muscle shows pronounced myofibrillar fragmentation and disorganization and increased number of mitochondria

increased myocardial fiber size ( J:113016 )

• individual cardiomyocytes are markedly increased in size

enlarged heart ( J:113016 )

• mice have grossly enlarged hearts at 9 weeks of age

cardiac hypertrophy ( J:113016 )

• 9-week old mice show significant increase in heart weight/tibial-length ratios

dilated cardiomyopathy ( J:113016 )

• mutants display severe dilated cardiomyopathy

decreased cardiac muscle contractility ( J:113016 )

• detectable by 4 weeks of age and progressively worsens

• significant decrease is shown by decreased percentage fractional shortening, decreased velocity of circumferential fiber shortening and reduced peak aortic outlflow velocity

• also, dP/dT_max and dP/dT_min are reduced significantly

abnormal heart ventricle pressure ( J:113016 )

• mutants have significant decrease in ventricular blood pressures

muscle

abnormal myocardial fiber morphology ( J:113016 )

• heart muscle shows pronounced myofibrillar fragmentation and disorganization and increased number of mitochondria

increased myocardial fiber size ( J:113016 )

• individual cardiomyocytes are markedly increased in size

dilated cardiomyopathy ( J:113016 )

• mutants display severe dilated cardiomyopathy

decreased cardiac muscle contractility ( J:113016 )

• detectable by 4 weeks of age and progressively worsens

• significant decrease is shown by decreased percentage fractional shortening, decreased velocity of circumferential fiber shortening and reduced peak aortic outlflow velocity

• also, dP/dT_max and dP/dT_min are reduced significantly

abnormal skeletal muscle fiber morphology ( J:113016 )

• myofibers from 3-month old mice display irregular contours

increased skeletal muscle fiber diameter ( J:113016 )

• myofiber cross-sectional area is reduced 2-fold in triceps of 3 month old mice vs littermate controls

decreased skeletal muscle mass ( J:113016 )

• male hemizygotes display significant loss of muscle mass at 3 months, becoming detectable at 10 weeks of age compared to littermate controls (Pdcd8-sufficent and non-transgenic hemizygotes)

muscle degeneration ( J:113016 )

• muscle degeneration is progressive, becoming detectable at 10 weeks of age; it is most apparent in fast-twitch muscles (gastrocnemium, triceps, quadriceps)

muscular atrophy ( J:113016 )

• all skeletal muscles analyzed including triceps, pectoralis, quadriceps, gluteus, and gastrocnemius muscles are significantly atrophied male hemizygotes

homeostasis/metabolism

increased circulating lactate level ( J:113016 )

• plasma lactate levels increase progressively with muscle loss

• a significant increase in lactate/pyruvate ratio is observed

abnormal glucose homeostasis ( J:113016 )

• mutant cardiomyocytes undergo compensatory metabolic switch toward glycolysis, and away from pyruvate utilization as result of impaired mitochondrial respiration

abnormal hormone level ( J:113016 )

• mutants show significant upregulation of atrial naturietic factor (ANF) and b-type natruietic peptide (BNP)

decreased catalase activity ( J:113016 )

• at 4.5 months of age, heart and skeletal muscle show significant reductions in catalase activity

behavior/neurological

lethargy ( J:113016 )

• loss of muscle mass results makes mice extremely lethargic by 5 months of age

Allelic Composition	Aifm1^tm2Pngr/Y Tmem163^{Tg(ACTB-cre)2Mrt}/0
Genetic Background	involves: 129P2/OlaHsd * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Aifm1^tm2Pngr mutation (0 available); any Aifm1 mutation (11 available)
Tmem163^{Tg(ACTB-cre)2Mrt} mutation (3 available); any Tmem163 mutation (37 available)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:113016 )

• male mutants are present at Mendelian ratios at E7.5 and 10.5, but no viable embryos are recovered after E12.5

embryo

embryonic growth retardation ( J:113016 )

• embryos between E7.5 and 10.5 exhibit severe growth retardation

growth/size/body

embryonic growth retardation ( J:113016 )

• embryos between E7.5 and 10.5 exhibit severe growth retardation

Allelic Composition	Aifm1^tm2Pngr/Aifm1⁺ Tmem163^{Tg(ACTB-cre)2Mrt}/0
Genetic Background	involves: 129P2/OlaHsd * FVB/N

Find Mice

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

mortality/aging

prenatal lethality, incomplete penetrance ( J:113016 )

• a percentage of female heterozygotes die during development; female mutants are born at a lower than expected frequency

growth/size/body

decreased body size ( J:113016 )

• females surviving through birth are smaller in size than wild-type littermates but appear healthy and fertile

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