Strain Name:
FVB.129S7(Cg)-Mcph1tm1.1Kali/Mmjax
Stock Number:
066770-JAX
Citation ID:
RRID:MMRRC_066770-JAX
Other Names:
MCPH1flox/flox

Strain Information

Mcph1tm1.1Kali
Name: microcephaly, primary autosomal recessive 1; targeted mutation 1.1, Kaiyi Li
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 8
Alteration at locus: Conditional
Mcph1
Name: microcephaly, primary autosomal recessive 1
Synonyms: BRIT1, 5430437K10Rik, D030046N04Rik
Type: Gene
Species: Mouse
Chromosome: 8
Alteration at locus: Conditional
NCBI: 244329
HGNC: HGNC:6954
Homologene: 32586
Genetic Alterations
The loxP sites are located in Intron 2 and 3 to eliminate Exon 2 when crossed with the mice with conditional expression of a Cre gene.
Genotype Determination
ES Cell Line

AB2.2 (129S7/SvEvBrd-Hprtb-m2)

Phenotype
The phenotype for Mcph1-floxed, congenic on FVB background (MCPH1flox/flox) and MCPH1+/flox is similar to wild-type.

After crossing with MMTV-cre, the mammary gland branching in females is significantly inhibited when compared to the wild-type mice during puberty and maturation.

Homozygous global knockout of Mcph1 (MCPH1-/-): infertile due to meiotic recombination repair defects (in male and female), several organs smaller than wild-type, irradiation sensitivity.

Heterozygous global knockout of Mcph1 (Mcph1+/-): normal growth, fertilizable, irradiation sensitivity in between.
MeSH Terms
  • Animals
  • Chromosomal Proteins, Non-Histone/genetics
  • Chromosomal Proteins, Non-Histone/metabolism
  • DNA Repair
  • Genomic Instability
  • Meiosis
  • Mice/genetics
  • Mice/metabolism
  • Mice, Knockout
  • Mitosis
  • Recombination, Genetic
  • Apoptosis
  • Breast Neoplasms/genetics
  • Breast Neoplasms/metabolism
  • Breast Neoplasms/pathology
  • Breast Neoplasms/physiopathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin E/genetics
  • Cyclin E/metabolism
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • Neoplastic Processes
  • RNA Interference
  • RNA, Small Interfering/genetics
  • RNA, Small Interfering/metabolism
  • Up-Regulation
  • Aneuploidy
  • Cell Transformation, Neoplastic/genetics
  • Cell Transformation, Neoplastic/pathology
  • Centrosome/metabolism
  • Chromosomal Proteins, Non-Histone/deficiency
  • Chromosome Aberrations
  • DNA Breaks, Double-Stranded
  • DNA Repair/genetics
  • Fibroblasts/metabolism
  • Genes, Tumor Suppressor/physiology
  • Genomic Instability/genetics
  • Homologous Recombination/genetics
  • Lymphoma/genetics
  • Lymphoma/metabolism
  • Lymphoma/pathology
  • Tumor Suppressor Protein p53
Strain Development
Mcph1 BAC clones were isolated from a 129/SvEv genomic library to construct the conditional targeting vector. A 0.5-kb fragment consisting of exon 2 (E2), 3′ end of intron 1 and 5′ end of intron 2 was inserted between two loxP sites in the targeting vector, which allows to remove E2 after introduction of Cre. A 3.0-kb fragment from intron 2 was cloned into the same vector as the 3′ homologous arm. A 5′ homologous arm (a 3.0-kb fragment containing E1 and 5′ of intron 1) was subsequently cloned into the vector. The Neo selection marker can be excised via the recombination of the Frt sites after introduction of Flp recombinase, which could avoid any unexpected effect of Neo cassette on the normal splicing of Mcph1.

The targeting vector was linearized by PacI and electroporated into AB2.2 ES cells. Neomycin-resistant colonies were selected with geneticin and analyzed for the expected homologous recombination by EcoRV digestion followed by Southern blot analysis using a 5′ flanking probe. The targeted clones were then confirmed using a 3′ flanking probe after BamHI digestion of the genomic DNA. To generate the mice with Mcph1 conditional targeting allele, two targeting ES cells were injected into C57BL/6J mouse blastocysts. Male chimeras with 95% agouti color were bred with C57BL/6J females and germ-line transmission of the Mcph1 targeting allele was confirmed by agouti coat color in F1 animals and by Southern blot analysis on mouse tail DNA using the two flanking probes for Mcph1.

The heterozygous mice were crossed with B6;SJL-Tg(ACTFLPe)9205Dym/J (RRID:IMSR_JAX:003800) to generate mice carrying one Mcph1 conditional allele with the excision of the Neo cassette (Mcph1+/flox). These mice were then bred with STOCK Tg(MMTV-cre)4Mam/J (RRID:IMSR_JAX:003553) to generate the conditional knockout mouse model.
Suggested Control Mice
FVB
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.
  • Cancer
  • Cell Biology
  • Models for Human Disease
  • Reproduction
Donor
Kaiyi Li, Ph.D., The University of Texas MD Anderson Cancer Center.
Shiaw-yih Lin, Ph.D., The University of Texas MD Anderson Cancer Center.
Primary Reference

Liang Y, Gao H, Lin SY, Peng G, Huang X, Zhang P, Goss JA, Brunicardi FC, Multani AS, Chang S, Li K. BRIT1/MCPH1 is essential for mitotic and meiotic recombination DNA repair and maintaining genomic stability in mice. PLoS Genet. 2010 Jan 22;6(1):e1000826. doi: 10.1371/journal.pgen.1000826. PMID: 20107607; PMCID: PMC2809772.

Liang Y, Gao H, Lin SY, Goss JA, Brunicardi FC, Li K. siRNA-based targeting of cyclin E overexpression inhibits breast cancer cell growth and suppresses tumor development in breast cancer mouse model. PLoS One. 2010 Sep 20;5(9):e12860. doi: 10.1371/journal.pone.0012860. (Medline PMID: 20877462)

Liang Y, Gao H, Lin SY, Goss JA, Du C, Li K. Mcph1/Brit1 deficiency promotes genomic instability and tumor formation in a mouse model. Oncogene. 2015 Aug 13;34(33):4368-78. doi: 10.1038/onc.2014.367. Epub 2014 Nov 3. (Medline PMID: 25362854)

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
White
Eye
Pink
MMRRC Breeding System
Backcross and Sib-mating
Generation
N7 (FVB, F24+
Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: 4 to 6 months 4 to 6 months
Bred to Homozygosity
Yes
Average litter size
4 to 6
Recommended wean age
3 Weeks
Average Pups Weaned
4 to 6

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.

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
066770-JAX-SPERM Cryo-preserved spermatozoa $437.00 / $437.00
Non-Profit / For-Profit
Aliquot Approximate quantity3
066770-JAX-RESUS Litter recovered from cryo-archive $2,022.00 / $2,022.00
Non-Profit / For-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.