Most Apaf1 knock-out mice exhibit a perinatal lethal phenotype with severe neuropathology. Surviving male mutants have massive degeneration of spermatogonia and reduced sperm.
Dr. Joachim Herz, Univ of Texas Southwest Med Ctr Dallas
Mice that are heterozygous for the targeted allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Most homozygous mutant mice have a perinatal lethal phenotype with severe neuropathology (exencephaly or cranioschesis). Five percent of homozygous null mice survive to weaning age with hydrocephalus, but do not survive much longer. Another five percent survive to adulthood and exhibit hyperactivity. Surviving male homozygotes are infertile. Homozygous female mice are fertile and have litters, but at a reduced frequency. Homozygous male mice are infertile due to massive degeneration of spermatogonia and reduced sperm. At age E9.5 in development neural tube closure defects and thickened neuropithelium appear. No targeted gene product (protein) was immunodetected in homozygous mutant mice. Fibroblast extracts from mutant adult mice do not activate caspase-3. This mutant mouse strain represents a model that may be useful in studies of the role of apoptotic cell death in disease processes.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the targeted gene with an arginine-to-glycine mutation at amino acid 111 and a stop codon inserted at amino acid 124. The construct was electroporated into 129S6/SvEv derived SM-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
|Allele Name||targeted mutation 1, Joachim Herz|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Apaf1, apoptotic peptidase activating factor 1|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Insertion of a neomycin casette into sequences encoding the Ced 4 homology domain corresponding to amino acid 111. Insertion disrupts the reading frame of the protein.|
|Mutations Made By|| |
Narimon Honarpour, Univ of Texas Southwestern Medical Ctr
The resulting chimeric animals were crossed to C57BL/6 female mice. The strain is maintained by heterozygous intercrossing. Expected coat color is: Agouti and Black.
When using the Apaf1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004373 in your Materials and Methods section.