hm1

Apaf1^{Gt(IRESBetageo)XIX18Pgr}/Apaf1^{Gt(IRESBetageo)XIX18Pgr}
involves: 129/Sv * 129X1/SvJ

Key:
♀	phenotype observed in females	WTSI	Wellcome Trust Sanger Institute
♂	phenotype observed in males	Euro	Europhenome
N	normal phenotype

cellular

abnormal apoptosis ( J:103480 )

• 5 Gy gamma-irradiation of CD4⁺CD8⁺ thymocytes from hosts reconstituted with Apaf1^{Gt(IRESBetageo)XIX18Pgr} homozygous fetal liver do not display caspase 2 cleavage while those derived from wildtype fetal liver do

hm2

Apaf1^{Gt(IRESBetageo)XIX18Pgr}/Apaf1^{Gt(IRESBetageo)XIX18Pgr}
involves: 129S1/Sv * 129X1/SvJ

Key:
♀	phenotype observed in females	WTSI	Wellcome Trust Sanger Institute
♂	phenotype observed in males	Euro	Europhenome
N	normal phenotype

nervous system

decreased neuron apoptosis ( J:112874 )

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

increased neuron apoptosis ( J:112874 )

• when cultured neurons express anchored form of Pdcd8 as well as endogenous Pdcd8, significant apoptosis is observed

cellular

decreased neuron apoptosis ( J:112874 )

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

increased neuron apoptosis ( J:112874 )

• when cultured neurons express anchored form of Pdcd8 as well as endogenous Pdcd8, significant apoptosis is observed

mortality/aging

complete lethality throughout fetal growth and development ( J:49840 )

• embryonic defects apparent by E12.5, die by E17

cellular

decreased apoptosis ( J:49840 )

• induction of apoptosis in mutant embryonic fibroblasts is similar to controls, but mutant fibroblasts show reduced cell death after prolonged treatment with apoptotic stimuli (anti-Fas antibody, C6-ceramide, and staurosporin)

• tissues that normally exhibit apoptosis in developmental stages instead exhibit hyperplasia and/or overgrowth

craniofacial

abnormal craniofacial bone morphology ( J:49840 )

impaired ossification of basisphenoid bone ( J:49840 )

absent neurocranium ( J:49840 )

• absence of skull vault

absent ethmoidal bone ( J:49840 )

absent vomer bone ( J:49840 )

persistence of medial edge epithelium during palatal shelf fusion ( J:49840 )

• late and imperfect palatial fusion occurs

midline facial cleft ( J:49840 )

nervous system

nervous system phenotype ( J:131954 )

N	• at E13-14 and E18, numbers of spinal motoneurons and dorsal root ganglion neurons are not different from wild-type (J:131954)

abnormal brain morphology ( J:49840 )

• brain hyperplasia presumably due to lack of apoptosis in the mantle layer of the developing diencephalon, midbrain, cerebellum and ventricular layer of the choroid plexus of the fourth ventricle; an excess of differentiating neurons is observed in these locations

abnormal brain development ( J:49840 )

abnormal embryonic neuroepithelial layer differentiation ( J:49840 )

• overgrowth resulting in abnormal folding and generation of a mantle layer

abnormal cortical marginal zone morphology ( J:49840 )

abnormal folding of telencephalic vesicles ( J:49840 )

• may be due to intense overgrowth (hyperplasia) of diencephalon and midbrain

small telencephalic vesicles ( J:49840 )

• may be due to intense overgrowth (hyperplasia) of diencephalon and midbrain

exencephaly ( J:49840 , J:131954 )

• rostral exencephaly (J:49840)

• forebrain exencephaly is observed in all animals (J:131954)

hydroencephaly ( J:49840 )

• results from obliteration of the lumen of the neural tube

choroid plexus hyperplasia ( J:49840 )

• hyperplasia of the choroid plexus of the fourth ventricle is seen

midbrain hyperplasia ( J:49840 )

hypothalamus hyperplasia ( J:49840 )

• abnormal overgrowth of ventral side of hypothalamus through the base of the skull

diencephalon hyperplasia ( J:49840 )

abnormal neuron morphology ( J:131954 )

• at E14 and E18, motoneurons and DRG neurons exhibit degenerative-like changes not seen in wild-type

abnormal neuron physiology ( J:131954 )

• at E14, developing neurons undergo atypical programmed cell death (PCD) in contrast to type 1 (apoptotic-like) mechanism exhibited in wild-type neurons; apoptotic-like degeneration markers (such as TUNEL labeling) are not observed in dying mutant neurons

vision/eye

abnormal lens polarity ( J:49840 )

small lens ( J:49840 )

persistence of hyaloid vascular system ( J:49840 )

• eye vascular endothelial cells obliterate the optic cup at E14.5

retina hyperplasia ( J:49840 )

• by E12.5, the retina is noticeably thicker

• by E14.5, the hyperplastic retina fills the optic cup and is folded

limbs/digits/tail

interdigital webbing ( J:49840 )

• interdigital webbing in limb buds with reduced apoptosis

skeleton

abnormal craniofacial bone morphology ( J:49840 )

impaired ossification of basisphenoid bone ( J:49840 )

absent neurocranium ( J:49840 )

• absence of skull vault

absent ethmoidal bone ( J:49840 )

absent vomer bone ( J:49840 )

digestive/alimentary system

persistence of medial edge epithelium during palatal shelf fusion ( J:49840 )

• late and imperfect palatial fusion occurs

embryogenesis

abnormal embryonic neuroepithelial layer differentiation ( J:49840 )

• overgrowth resulting in abnormal folding and generation of a mantle layer

ht4

Apaf1^fog/Apaf1^{Gt(IRESBetageo)XIX18Pgr}
involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C3H/HeJ * NMRI

Key:
♀	phenotype observed in females	WTSI	Wellcome Trust Sanger Institute
♂	phenotype observed in males	Euro	Europhenome
N	normal phenotype

nervous system

decreased neuron apoptosis ( J:131954 )

• dying motoneurons are rarely observed at E14 and E18, unlike in wild-type animals

abnormal neuron morphology ( J:131954 )

• neurons display characteristics of type 2 (autophagic) programmed cell death, in contrast to type 1 (apoptotic) PCD seen in wild-type

motor neuron degeneration ( J:131954 )

• motoneurons have normal nuclei and atypical cytoplasm, with structures having characteristics of lysosomes; cytoplasmic organelles appear aggregated in area with many lysosomes and autophagosomes

• mitochondria show loss of cristae and swollen rounded appearance; rough endoplasmic reticulum is dilated and Golgi is hypertrophic

• as degeneration proceeds, nucleus and cytoplasm become more condensed; at late stages, nucleus is condensed but remains intact

cellular

decreased neuron apoptosis ( J:131954 )

• dying motoneurons are rarely observed at E14 and E18, unlike in wild-type animals

cn5

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

Key:
♀	phenotype observed in females	WTSI	Wellcome Trust Sanger Institute
♂	phenotype observed in males	Euro	Europhenome
N	normal phenotype

cellular

decreased neuron apoptosis ( J:112874 )

• neurons show increased survival vs wild-type after camptothecin treatment (J:112874)

• neurons cultured in pyruvate supplemented media show increased survival after camptothecin treatment (J:112874)

• expression of anchored Pdcd8 does not provide further protection from death to neurons (J:112874)

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 (J:112874)

abnormal mitochondrial physiology ( J:112874 )

• cultured neurons can maintain oxygen consumption after camptothecin treatment if anchored Pdcd8 is expressed (J:112874)

nervous system

decreased neuron apoptosis ( J:112874 )

• neurons show increased survival vs wild-type after camptothecin treatment (J:112874)

• neurons cultured in pyruvate supplemented media show increased survival after camptothecin treatment (J:112874)

• expression of anchored Pdcd8 does not provide further protection from death to neurons (J:112874)

increased neuron apoptosis ( J:112874 )

thickened cerebral cortex ( J:112874 )

• cortex is thickened compared to Pdcd8 conditional embryos (J:112874)

cx6

Aifm1^Hq/Aifm1^Hq
Apaf1^{Gt(IRESBetageo)XIX18Pgr}/Apaf1^{Gt(IRESBetageo)XIX18Pgr}
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

Key:
♀	phenotype observed in females	WTSI	Wellcome Trust Sanger Institute
♂	phenotype observed in males	Euro	Europhenome
N	normal phenotype

nervous system

decreased neuron apoptosis ( J:98103 )

• reduced apoptosis of cultured cortical neurons resulting from treatment with camptothecin (J:98103)

• neurons show enhanced viability when treated with camptothecin (J:98103)

• only about half of dying cells exhibit DNA fragmentation (J:98103)

cellular

decreased neuron apoptosis ( J:98103 )

• reduced apoptosis of cultured cortical neurons resulting from treatment with camptothecin (J:98103)

• neurons show enhanced viability when treated with camptothecin (J:98103)

• only about half of dying cells exhibit DNA fragmentation (J:98103)