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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Apaf1tm1Mak
targeted mutation 1, Tak W Mak
MGI:1928692
Summary 4 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Apaf1tm1Mak/Apaf1tm1Mak either: (involves: 129P2/OlaHsd * C57BL/6) or (involves: 129P2/OlaHsd * CD-1) MGI:2175700
hm2
Apaf1tm1Mak/Apaf1tm1Mak involves: 129P2/OlaHsd * CD-1 MGI:3783548
ht3
Apaf1fog/Apaf1tm1Mak involves: 129S6/SvEvTac * C3H/HeJ * CD-1 MGI:3783543
cx4
Apaf1tm1Mak/Apaf1tm1Mak
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 MGI:3699923


Genotype
MGI:2175700
hm1
Allelic
Composition
Apaf1tm1Mak/Apaf1tm1Mak
Genetic
Background
either: (involves: 129P2/OlaHsd * C57BL/6) or (involves: 129P2/OlaHsd * CD-1)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apaf1tm1Mak mutation (1 available); any Apaf1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• at E18.5, homozygotes are present at reduced frequencies, suggesting that some mutants, esp. those with a cauliflower-like mass on the face or a cone-shaped head mass with exencephalus die prenatally, possibly due to secondary effects such as hydrocephalus
• however, at E11.5 to E16.5, homozygotes are viable, of normal size, and present at the expected Mendelian ratios
• most homozygotes are found dead at birth or die within 12 hrs after birth, possibly due to the mechanical disruption of brain masses during delivery
• 3 out of 190 homozygotes exhibiting ectopic forebrain masses on the forehead survive until 10 days after birth

craniofacial
• at >E12.5, most homozygotes exhibit craniofacial anomalies including: (i) ectopic forebrain masses on the forehead (least severe); (ii) a cauliflower-like mass on the face; and (iii) a cone-shaped head mass with exencephalus
• these three phenotypes are detected at similar frequencies, irrespective of genetic background
• at >E12.5, a portion of homozygotes display ectopic forebrain protrusions on the forehead, with a thickened mitotic ventricular zone
• in newborn homozygotes, such forebrain masses are both hemorrhagic and necrotic
• at >E12.5, a portion of homozygotes display a cauliflower-like mass on the face, which is histologically identifed as forebrain tissue
• at >E12.5, a portion of homozygotes display a cone-shaped head mass and exencephalus
• at >E12.5, homozygotes with a cauliflower-like mass on the face exhibit an abnormally small, flat head

skeleton
• at >E12.5, a portion of homozygotes display ectopic forebrain protrusions on the forehead, with a thickened mitotic ventricular zone
• in newborn homozygotes, such forebrain masses are both hemorrhagic and necrotic

nervous system
• at >E12.5, homozygotes with a cauliflower-like mass on the face exhibit significant hyperplasia of the choroid plexus
• at >E12.5, homozygotes with a cauliflower-like mass on the face exhibit occlusion of the third ventricle
• at >E12.5, homozygotes with a cauliflower-like mass on the face exhibit a wedge-shaped deformity of the hypothalamus
• at >E12.5, homozygotes with a cauliflower-like mass on the face contain supernumerary hypothalamic cells, with increased mitotic activity noted up to E16.5
• at >E12.5, homozygotes with a cauliflower-like mass on the face exhibit a wedge-shaped deformity of the thalamus
• at >E12.5, homozygotes with a cauliflower-like mass on the face contain supernumerary thalamic cells, with increased mitotic activity noted up to E16.5
• at >E12.5, homozygotes with a cauliflower-like mass on the face exhibit thickening of the cortex despite a normal layering pattern
• at >E12.5, homozygotes with a cone-shaped head mass and exencephay display a significantly enlarged hindbrain
• at >E12.5, homozygotes with a cone-shaped head mass exhibit exencephay, with ectopic protrusions resulting from overgrown thalamic areas

cellular
• ES cells, embryonic fibroblasts, and thymocytes isolated from homozygous mutant mice show some resistance to various apoptotic stimuli (anisomycin, cisplatinum, etoposide, UV irradiation, gamma-irradiation, or dexamethasone)
• in contrast, thymocytes and activated peripheral T-lymphocytes exhibit normal susceptibility to Fas-mediated cell death
• also, mutant embryonic fibroblasts show normal cytochrome c release in response to etoposide, staurosporine, or UV irradiation
• at E14.5, homozygotes exhibit significantly reduced apoptosis in the hindbrain, the roof of midbrain, and cortex of forebrain
• homozygotes show significantly increased BrdU incorporation in affected brain regions, such as in the hindbrain at E12.5, the forebrain at E13.5, and the hyperplastic thalamic areas at E14.5
• mutant thymocytes are resistant to the loss of mitochondrial transmembrane potential following treatment with dexamethasone, etoposide, staurosporine, or gamma-irradiation; moreover, activation of caspase-2, -3, and -8 is reduced in response to these apoptotic signals
• in contrast, mutant thymocytes exhibit normal loss of mitochondrial transmembrane potential in response to Fas-mediated apoptosis, in the absence of impaired caspase-2, -3, and -8 activation

limbs/digits/tail
• mutant embryos exhibit poorly shaped digits
• homozygotes display a delay in removal of interdigital webs of forelimbs at E13.5 (4 out of 16) and of hindlimbs at E14.5 (4 out of 12)
• however, all homozygotes reassume normal digit development and removal of interdigital webs at >E15.5

immune system
N
• the few homozygotes that survive until 10 days after birth display normal thymocyte development relative to wild-type mice

hearing/vestibular/ear
N
• at E18.5, homozygotes display a normal morphology of inner ear sensory epithelia relative to wild-type mice

growth/size/body
• at >E12.5, a portion of homozygotes display a cauliflower-like mass on the face, which is histologically identifed as forebrain tissue
• at >E12.5, a portion of homozygotes display a cone-shaped head mass and exencephalus
• at >E12.5, homozygotes with a cauliflower-like mass on the face exhibit an abnormally small, flat head
• at >E12.5, homozygotes with a cauliflower-like mass on the face exhibit an abnormally small, flat head




Genotype
MGI:3783548
hm2
Allelic
Composition
Apaf1tm1Mak/Apaf1tm1Mak
Genetic
Background
involves: 129P2/OlaHsd * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apaf1tm1Mak mutation (1 available); any Apaf1 mutation (78 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
N
• at E13-14 and E18, numbers of spinal motoneurons and dorsal root ganglion neurons are not different from wild-type
• forebrain exencephaly is observed in all animals
• 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




Genotype
MGI:3783543
ht3
Allelic
Composition
Apaf1fog/Apaf1tm1Mak
Genetic
Background
involves: 129S6/SvEvTac * C3H/HeJ * CD-1
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apaf1fog mutation (1 available); any Apaf1 mutation (78 available)
Apaf1tm1Mak mutation (1 available); any Apaf1 mutation (78 available)
phenotype observed in females
phenotype observed in males
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




Genotype
MGI:3699923
cx4
Allelic
Composition
Apaf1tm1Mak/Apaf1tm1Mak
Rb1tm1Tyj/Rb1tm1Tyj
Tg(Rb1)1Blg/0
Genetic
Background
involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apaf1tm1Mak mutation (1 available); any Apaf1 mutation (78 available)
Rb1tm1Tyj mutation (5 available); any Rb1 mutation (106 available)
Tg(Rb1)1Blg mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hearing/vestibular/ear
• at E18.5, mutant mice display a similar extent of cochlear hair cell overproduction relative to mice that are homozygous for Rb1tm1Tyj and hemizygous for Tg(Rb1)#Blg
• at E18.5, mutant mice display a similar extent of vestibular hair cell overproduction relative to mice that are homozygous for Rb1tm1Tyj and hemizygous for Tg(Rb1)#Blg

nervous system
• at E18.5, mutant mice display a similar extent of cochlear hair cell overproduction relative to mice that are homozygous for Rb1tm1Tyj and hemizygous for Tg(Rb1)#Blg
• at E18.5, mutant mice display a similar extent of vestibular hair cell overproduction relative to mice that are homozygous for Rb1tm1Tyj and hemizygous for Tg(Rb1)#Blg





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last database update
04/30/2024
MGI 6.23
The Jackson Laboratory