Phenotypes Associated with This Genotype

Genotype
MGI:3687280

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

• ♀: 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)