Strain Name:
129S.Cg-Macroh2a2tm1.1Peh Macroh2a1tm1Peh/Mmjax
Stock Number:
037356-JAX
Citation ID:
RRID:MMRRC_037356-JAX
Other Names:
macroH2A1/2 double knockout

Strain Information

Macroh2a1tm1Peh
Name: macroH2A.1 histone; targeted mutation 1, John R Pehrson
Synonyms: macroH2A1-
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 13
Alteration at locus: Knockout
Macroh2a2tm1.1Peh
Name: macroH2A.2 histone; targeted mutation 1.1, John R Pehrson
Synonyms: macroH2A2 KO
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 10
Alteration at locus: Knockout
Macroh2a1
Name: macroH2A.1 histone
Synonyms: MACROH2A1.2, H2afy, H2AF12M, mH2a1
Type: Gene
Species: Mouse
Chromosome: 13
Alteration at locus: Knockout
NCBI: 26914
HGNC: HGNC:4740
Homologene: 3598
Macroh2a2
Name: macroH2A.2 histone
Synonyms: H2afy2
Type: Gene
Species: Mouse
Chromosome: 10
Alteration at locus: Knockout
NCBI: 404634
Homologene: 10246
Genetic Alterations
  • H2afytm1Peh: An IRESBgeo cassette was inserted in first intron. This cassette was flanked by loxP sites and a third loxP site was inserted in the second intron. Transient cre expression removed the floxed sequence, including exon 2, which encodes the first part of the H2A domain.
  • H2afy2tm1.1Peh: The Neo cassette was flanked by loxP recombination sites and inserted into an EaeI site located less than 300 bp upstream of exon 2. A third loxP site was inserted into an EaeI site located less than 150 bp downstream of exon 2. Cre excision was used to remove the floxed sequence, including exon 2.

These double knockout mice exhibit reduced lean body mass, shortened body length, an abnormally large eyelid opening (macroblepharon), and darkened back fur. They may be useful for studying the involvement of H2A histones in the regulation of gene expression.


ES Cell Line
  • H2afytm1Peh: Not specified derived from 129X1/SvJ
  • H2afy2tm1.1Peh: v6.5 derived from (C57BL/6 x 129S4/SvJae)F1
Phenotype

Macroh2a1 (H2afy) and Macroh2a2 (H2afy2) or macroH2A1/2 (H2A histone family, member Y and Y2, respectively), encode an alternative H2A histone that includes a unique C-terminal non-histone domain. The macroH2A histones function in a subset of nucleosomes where they are involved in the regulation of gene expression. Mice homozygous for both alleles are viable and fertile, but exhibit reduced lean body mass and are shorter in length than wild type controls. Mice remain small throughout adulthood. On the 129S6 background, double KO mice exhibit an abnormally large eyelid opening (macroblepharon), some eyelid inflammation, and darkened fur on the back (by 6 weeks of age). Double mutant mice on the C57BL/6 background breed poorly by either failing to reproduce or exhibiting high rates (29%) of perinatal lethality. This strain may be useful for studying the involvement of H2A histones in the regulation of gene expression.

Mammalian Phenotype Terms
Allelic Composition: H2afytm1Peh/H2afytm1Peh (Genetic Background: B6.129X1-H2afytm1Peh )

Allelic Composition: (Genetic Background: )

  • normal phenotype
MeSH Terms
  • Animals
  • Animals, Newborn
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Silencing
  • Glucose/metabolism
  • Histones/biosynthesis
  • Histones/genetics
  • Liver/metabolism
  • Mice
  • Mice, Knockout
  • Mutation
  • Nucleosomes/genetics
  • Nucleosomes/metabolism
  • X Chromosome/genetics
  • X Chromosome/metabolism
  • X Chromosome Inactivation/genetics
  • X Chromosome Inactivation/physiology
Strain Development
The Macroh2a1 (H2afy2) targeting vector was designed to insert a loxP-flanked PGKneo cassette upstream of exon 2 and loxP site downstream of exon 2. Exon 2 includes the initiation codon and encodes the first 57 amino acids of the histone region. The construct was electroporated into (C57BL/6 x 129S4/SvJae)F1-derived v6.5 embryonic stem (ES) cells. The resulting chimeric animals were mated to C57BL/6 mice and progeny crossed to mice carrying Tg(EIIa-cre)C5379Lmgd (on an unspecified background) to remove exon 2 and the neo casstte. Offspring were backcrossed to 129S6/SvEvTac for at least 10 generations.

The Macroh2a2 (H2afy) targeting vector was designed to insert a loxP-flanked IRESBgeo cassette upstream of exon 2 and loxP site downstream of exon 2. Exon 2 includes the initiation codon and encodes the first part of the H2A domain. The construct was electroporated into a 129X1/SvJ-derived embryonic stem (ES) cells. Transient cre expression removed the floxed sequence. The resulting chimeric animals were mated to C57BL/6 mice and progeny backcrossed to 129S6/SvEvTac for at least 10 generations.

H2afy (MMRRC #037472) and H2afy2 (MMRRC #037474)-deficient mice were combined to generate a double knockout. The donating investigator maintains the strain as a homozygous double knockout. Upon arrival, mice were bred to 129S1/SvImJ for at least 1 generation to establish the colony.
Suggested Control Mice
Wild-type littermates
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.
  • Developmental Biology
  • Metabolism
  • Research Tools
Donor
John Pehrson, Ph.D., University of Pennsylvania.
Primary Reference

Changolkar LN, Costanzi C, Leu NA, Chen D, McLaughlin KJ and Pehrson JR. Developmental changes in histone macroH2A1-mediated gene regulation. Mol Cell Biol. 2007 Apr;27(7):2758-64. Epub 2007 Jan 22. (Medline PMID:17242180)

Colony and Husbandry Information

Fertility may decrease more rapidly than wild-type 129 mice, so mice are typically bred when they are less than 4 months.

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
Agouti
Other
Many double knockout become darker on their back than wild-type controls at around 6 weeks of age.
MMRRC Breeding System
Sib-mating
Breeding Scheme(s)
  • Wild-type female x Heterozygous male littermate or reciprocal mating
  • Homozygous female x Homozygous male littermate
Generation
N10
Overall Breeding Performance
Good, per donating investigator: the fertility of the mutants may decrease more rapidly than wild-type 129 mice, so we typically breed them when they are young, less than 4 months.
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Reduced Reduced Fertility may decrease more rapidly than wild-type 129 mice, so mice are typically bred when they are less than 4 months.
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Average litter size
4-6
Recommended wean age
3 weeks

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
037356-JAX-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
037356-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.