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Imprinted expression of the H19 and Igf2 loci is dependent upon a differentially methylated domain (DMD or Rr27) that coordinates the reciprocal maternal/paternal expression of H19 and Igf2 by controlling access to shared enhancers. Specifically, on the maternal allele, the DMD acts as a methylation-sensitive insulator that results in H19 expression and Igf2 inactivation. The four CpG-rich regions in the DMD bind CCCTC-binding factor (CTCF) on the hypomethylated maternal allele, subsequently blocking the Igf2 gene from the enhancers shared by H19 and Igf2. On the paternal allele, the hypermethylation of DMD concomitantly methylates H19, resulting in H19 inactivation and Igf2 expression. The DMRflox mice have loxP sites flanking the H19/Igf2 imprinting control region, at -6.5 to -0.8kb upstream of the H19 major start site.Mice homozygous for the DMRflox allele are viable and fertile. After Cre recombinase-deletion of the floxed DMD region, the resulting mice exhibit tissue-specific disruption of imprinted expression of H19 and Igf2. The donating laboratory notes that upon Cre-mediated recombination on the maternal chromosome there is a phenotype that mimics Beckwith Wiedemann syndrome. Maternal Igf2 expression is activated so that overall there is 2X expression of Igf2 and maternal H19 expression is reduced by 4-50-fold in a tissue dependent manner. Together, these expression changes result in a series of phenotypes including fetal overgrowth, cancer susceptibility, and cardiac insufficiency in aged mice.These DMRflox mice may be useful for studying the chromatin interactions and epigenetics involved in H19/Igf2 imprinting.
To request gene-specific and other genotyping services for a strain, please contact the distribution MMRRC Center for more information.
The MMRRC has developed a Genetic Quality Control pipeline using the MiniMUGA array to provide additional information to identify and validate genetic backgrounds of MMRRC strains. For more information on whether genetic background data is available, please contact MMRRC_GeneticQC@med.unc.edu. Note: that MiniMUGA genetic background data is not available on all strains, but can be ordered if desired.
Srivastava M, Hsieh S, Grinberg A, Williams-Simons L, Huang SP, Pfeifer K. H19 and Igf2 monoallelic expression is regulated in two distinct ways by a shared cis acting regulatory region upstream of H19. Genes Dev. 2000 May 15;14(10):1186-95. (Medline PMID: 10817754)
Disclaimer: If MMRRC Strain Genetic Quality Control (GQC; based on MiniMUGA genotyping and analysis) has been completed for this strain, the information might differ from the genetic background information provided by the submitter. MiniMUGA genetic analysis is done on a strain’s tissue samples taken when archived by or ordered from the assigned MMRRC Center.
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.
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.
A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Nathan Whitman.
A Commercial License Agreement from the Submitter is required for for-profit entities to use this strain. For more information, please contact Nathan Whitman
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.
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.
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