Mouse Genome Informatics
hm1
    Apaf1Gt(IRESBetageo)XIX18Pgr/Apaf1Gt(IRESBetageo)XIX18Pgr
involves: 129/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• 5 Gy gamma-irradiation of CD4+CD8+ thymocytes from hosts reconstituted with Apaf1Gt(IRESBetageo)XIX18Pgr homozygous fetal liver do not display caspase 2 cleavage while those derived from wildtype fetal liver do


Mouse Genome Informatics
hm2
    Apaf1Gt(IRESBetageo)XIX18Pgr/Apaf1Gt(IRESBetageo)XIX18Pgr
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• cultured neurons show increased survival vs wild-type after camptothecin treatment
• when cultured neurons express anchored form of Pdcd8 as well as endogenous Pdcd8, significant apoptosis is observed

cellular
• cultured neurons show increased survival vs wild-type after camptothecin treatment
• when cultured neurons express anchored form of Pdcd8 as well as endogenous Pdcd8, significant apoptosis is observed


Mouse Genome Informatics
hm3
    Apaf1Gt(IRESBetageo)XIX18Pgr/Apaf1Gt(IRESBetageo)XIX18Pgr
involves: 129S1/Sv * 129X1/SvJ * NMRI
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• embryonic defects apparent by E12.5, die by E17

cellular
• 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
• absence of skull vault
• late and imperfect palatial fusion occurs

nervous system
N
• at E13-14 and E18, numbers of spinal motoneurons and dorsal root ganglion neurons are not different from wild-type (J:131954)
• 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
• overgrowth resulting in abnormal folding and generation of a mantle layer
• may be due to intense overgrowth (hyperplasia) of diencephalon and midbrain
• may be due to intense overgrowth (hyperplasia) of diencephalon and midbrain
• rostral exencephaly (J:49840)
• forebrain exencephaly is observed in all animals (J:131954)
• results from obliteration of the lumen of the neural tube
• hyperplasia of the choroid plexus of the fourth ventricle is seen
• abnormal overgrowth of ventral side of hypothalamus through the base of the skull
• at E14 and E18, motoneurons and DRG neurons exhibit degenerative-like changes not seen in wild-type
• 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
• eye vascular endothelial cells obliterate the optic cup at E14.5
• 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 in limb buds with reduced apoptosis

skeleton
• absence of skull vault

digestive/alimentary system
• late and imperfect palatial fusion occurs

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

growth/size
• late and imperfect palatial fusion occurs


Mouse Genome Informatics
ht4
    Apaf1fog/Apaf1Gt(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 EuPh Europhenome
N normal phenotype
nervous system
• dying motoneurons are rarely observed at E14 and E18, unlike in wild-type animals
• neurons display characteristics of type 2 (autophagic) programmed cell death, in contrast to type 1 (apoptotic) PCD seen in wild-type
• 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
• dying motoneurons are rarely observed at E14 and E18, unlike in wild-type animals


Mouse Genome Informatics
cn5
    Apaf1Gt(IRESBetageo)XIX18Pgr/Apaf1Gt(IRESBetageo)XIX18Pgr
Foxg1tm1(cre)Skm/Foxg1+
Aifm1tm2Pngr/Y

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• 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)
• 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)
• cultured neurons can maintain oxygen consumption after camptothecin treatment if anchored Pdcd8 is expressed (J:112874)

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


Mouse Genome Informatics
cx6
    Aifm1Hq/Aifm1Hq
Apaf1Gt(IRESBetageo)XIX18Pgr/Apaf1Gt(IRESBetageo)XIX18Pgr

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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
• 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)