Phenotypes associated with this allele

• Allele Symbol: Apaf1^{Gt(IRESBetageo)XIX18Pgr}
• Allele Name: gene trap XIX18, Peter Gruss
• Allele ID: MGI:1857868
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Apaf1^Gt(IRESBetageo)XIX18Pgr/Apaf1^Gt(IRESBetageo)XIX18Pgr	involves: 129S1/Sv * 129X1/SvJ	MGI:3687282
hm2	Apaf1^Gt(IRESBetageo)XIX18Pgr/Apaf1^Gt(IRESBetageo)XIX18Pgr	involves: 129S1/Sv * 129X1/SvJ * NMRI	MGI:3588510
hm3	Apaf1^Gt(IRESBetageo)XIX18Pgr/Apaf1^Gt(IRESBetageo)XIX18Pgr	involves: 129/Sv * 129X1/SvJ	MGI:3610484
ht4	Apaf1^fog/Apaf1^Gt(IRESBetageo)XIX18Pgr	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C3H/HeJ * NMRI	MGI:3783544
cn5	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
cx6	Aifm1^Hq/Aifm1^Hq Apaf1^Gt(IRESBetageo)XIX18Pgr/Apaf1^Gt(IRESBetageo)XIX18Pgr	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3699821

Genotype
MGI:3687282

hm1

• Allelic Composition: Apaf1^{Gt(IRESBetageo)XIX18Pgr}/Apaf1^{Gt(IRESBetageo)XIX18Pgr}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

Genotype
MGI:3588510

hm2

• Allelic Composition: Apaf1^{Gt(IRESBetageo)XIX18Pgr}/Apaf1^{Gt(IRESBetageo)XIX18Pgr}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * NMRI

mortality/aging

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

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

cellular

decreased fibroblast 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)

craniofacial

abnormal craniofacial bone morphology ( J:49840 )

impaired ossification of basisphenoid bone ( J:49840 )

absent neurocranium ( J:49840 )

• absence of skull vault

absent ethmoid 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:49840 )

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

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 embryonic telencephalon ( J:49840 )

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

hydrocephaly ( J:49840 )

• results from obliteration of the lumen of the neural tube

midbrain hyperplasia ( J:49840 )

choroid plexus hyperplasia ( J:49840 )

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

hypothalamus hyperplasia ( J:49840 )

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

diencephalon hyperplasia ( J:49840 )

exencephaly ( J:49840 , J:131954 )

• rostral exencephaly (J:49840)

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

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 fold ( J:49840 )

• by E14.5, the hyperplastic retina is folded

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 ethmoid 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

embryo

abnormal embryonic tissue morphology ( J:49840 )

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

abnormal embryonic neuroepithelial layer differentiation ( J:49840 )

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

growth/size/body

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

• late and imperfect palatial fusion occurs

midline facial cleft ( J:49840 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Noonan syndrome		DOID:3490	OMIM:PS163950	J:49840

Genotype
MGI:3610484

hm3

• Allelic Composition: Apaf1^{Gt(IRESBetageo)XIX18Pgr}/Apaf1^{Gt(IRESBetageo)XIX18Pgr}
• Genetic Background: involves: 129/Sv * 129X1/SvJ

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

Genotype
MGI:3783544

ht4

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

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

Genotype
MGI:3687281

cn5

• 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

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 )

♂ • 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

thickened cerebral cortex ( J:112874 )

♂ • cortex is thickened compared to Pdcd8 conditional embryos

Genotype
MGI:3699821

cx6

• Allelic Composition: Aifm1^Hq/Aifm1^Hq; Apaf1^{Gt(IRESBetageo)XIX18Pgr}/Apaf1^{Gt(IRESBetageo)XIX18Pgr}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

nervous system

decreased neuron apoptosis ( J:98103 )

♀ • reduced apoptosis of cultured cortical neurons resulting from treatment with camptothecin

♀ • neurons show enhanced viability when treated with camptothecin

♀ • only about half of dying cells exhibit DNA fragmentation

cellular

decreased neuron apoptosis ( J:98103 )

♀ • reduced apoptosis of cultured cortical neurons resulting from treatment with camptothecin

♀ • neurons show enhanced viability when treated with camptothecin

♀ • only about half of dying cells exhibit DNA fragmentation