Strain Name:
B6J.129P2-Apaf1tm1Mak/Mmjax
Stock Number:
044042-JAX
Citation ID:
RRID:MMRRC_044042-JAX
Other Names:
Apaf1 WT X +/- B6F10

Strain Information

Apaf1tm1Mak
Name: apoptotic peptidase activating factor 1; targeted mutation 1, Tak W Mak
Synonyms: apaf1-, Apaf1tm1Ari
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 10
Alteration at locus: Knock-In
Apaf1
Name: apoptotic peptidase activating factor 1
Synonyms: 6230400I06Rik, Apaf1l
Type: Gene
Species: Mouse
Chromosome: 10
Alteration at locus: Knock-In
NCBI: 11783
HGNC: HGNC:576
Homologene: 7626
Genetic Alterations
An exon encoding a portion of the nucleotide-binding P loop of Apaf1 was deleted with Neo insertion in the sense orientation.
ES Cell Line
E14K derived from 129P2/OlaHsd
Phenotype
Apaf1-deficient mice exhibited reduced apoptosis in the brain and striking craniofacial abnormalities with hyperproliferation of neuronal cells. Apaf1-deficient cells were resistant to a variety of apoptotic stimuli, and the processing of Caspases 2, 3, and 8 was impaired. However, both Apaf1-/- thymocytes and activated T lymphocytes were sensitive to Fas-induced killing, showing that Fas-mediated apoptosis in these cells is independent of Apaf1. These data indicate that Apaf1 plays a central role in the common events of mitochondria-dependent apoptosis in most death pathways and that this role is critical for normal development.
Mammalian Phenotype Terms
Allelic Composition: (Genetic Background: )

MeSH Terms
  • Animals
  • Apoptosis/physiology
  • Apoptotic Protease-Activating Factor 1
  • Brain/cytology
  • Brain/embryology
  • Brain Chemistry/physiology
  • Caspase 2
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases
  • Cells, Cultured
  • Cysteine Endopeptidases/metabolism
  • Cytochrome c Group/metabolism
  • Embryo, Mammalian/abnormalities
  • Enzyme Precursors/metabolism
  • Fibroblasts/cytology
  • Fibroblasts/enzymology
  • Gene Expression
  • Head/abnormalities
  • Membrane Potentials/physiology
  • Mice
  • Mice, Knockout
  • Mitochondria/enzymology
  • Phenotype
  • Proteins/genetics
  • Proteins/immunology
  • Proteins/metabolism
  • Skin Abnormalities
  • Stem Cells/cytology
  • Stem Cells/metabolism
  • T-Lymphocytes/chemistry
  • T-Lymphocytes/cytology
  • T-Lymphocytes/radiation effects
  • Thymus Gland/chemistry
  • Thymus Gland/cytology
  • Thymus Gland/radiation effects
  • Ultraviolet Rays
  • fas Receptor/physiology
Strain Development
Murine Apaf1 gene fragments were cloned from a 129/J genomic DNA library using a PCR-amplified human APAF1 cDNA probe. Primers used for amplification of human APAF1 cDNA commenced at positions 909 and 1321 (5′-GGC CAG TTG TTT TTG TCA A-3′ and 5′-CTG GTT GTA AGA AGA ATC-3′). Five overlapping phage genomic clones containing exons encoding Walker A and Walker B nucleotide-binding P-loop domains (PMID:6329717) were isolated. A targeting vector was designed to replace a 4.0-kb genomic fragment containing an exon encoding a portion of the P loop with a neomycin resistance cassette. The neomycin resistance gene (neo) was inserted in the targeting vector in the sense orientation to Apaf1 transcription, such that neo was flanked on the 3′ side by 0.8 kb of genomic DNA and on the 5′ side by 4 kb of genomic DNA. The targeting vector was linearized with XhoI and electroporated into E14K ES cells. After G418 selection (200 μg/ml, GIBCO-BRL), homologous recombinants were identified by PCR using a specific primer pair (5′-GGG CCA GCT CAT TCC TC-3′ and 5′-CAC TCT AGT GTC CAG GCT ATC-3′) and confirmed by Southern blotting according to standard protocols. Clones heterozygous for the targeted mutation were injected into 3.5-day C57BL/6 blastocysts, which were subsequently transferred into pseudopregnant foster mothers. Chimeric mice were crossed into strains C57BL/6 to produce heterozygous mutant mice. Germline transmission of the mutation was verified by PCR and Southern blot analysis of tail DNA. The null phenotype of Apaf1−/− mice was confirmed by Northern blot analysis. Apaf 1+/- mice were backcrossed 9 times into C57BL/6J mice from Jackson (JAX Strain #000664).
Suggested Control Mice
Apaf1+/+ and Apaf1+/-
MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact csmmrrc@jax.org. Older strains may not have this information.
  • Apoptosis
  • Cell Biology
  • Developmental Biology
  • Immunology and Inflammation
  • Neurobiology
Donor
Tak Mak, Ph.D Campbell Family Institute for Breast Cancer Research
Primary Reference

Yoshida H, Kong YY, Yoshida R, Elia AJ, Hakem A, Hakem R, Penninger JM, MakTW. Apaf1 is required for mitochondrial pathways of apoptosis and braindevelopment. Cell. 1998 Sep 18;94(6):739-50. (Medline PMID: 9753321)

Colony and Husbandry Information

Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-reports.

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email csmmrrc@jax.org.
Coat Color
Black
Eye
Black
MMRRC Breeding System
Random intra-strain mating
Generation
N10
Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: No No
Homozygotes are fertile: No No
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Greater than 12 months Greater than 12 months
Average litter size
4-6
Recommended wean age
3 Weeks
Average Pups Weaned
Less than 4

Order Request Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
044042-JAX-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
044042-JAX-RESUS Litter recovered from cryo-archive $2,022.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.