Phenotypes Associated with This Genotype

Genotype
MGI:3588510

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

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

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