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Strain Name:
B6.D2-Kmt2cem1Kaig Kmt2dem1Kaig/Mmjax
Stock Number:
076149-JAX
Citation ID:
RRID:MMRRC_076149-JAX
Other Names:
MLL3-KI/+;MLL4-KI/+

Strain Information

QUALITY CONTROL OF B6.D2-Kmt2cem1Kaig Kmt2dem1Kaig/Mmjax  |  The Jackson Laboratory
Last Updated:
Strain Data and Information Information by Submitter Assessed by MMRRC1,2
Published Provided
Allele-specific genotype3n.d.
Genetic backgroundn.d.
Viability of genotypes available for distributionn.d.
Specific Pathogen- Status n.d.
Recoverability of cryopreserved sperm/embryos4 n.d.
Gene or allele sequence3 n.d.
Gene or allele expression3n.d.
Gene or allele function3n.d.
Observable and/or measurable phenotypesn.d.
Fertility of genotypes available for distributionn.d.
Fecundity/breeding performancen.d.

1 When indicated as "assessed by MMRRC" ("YES"), please note that the information presented on this strain is to the best of our knowledge correct and up-to-date at the the MMRRC Distribution Center assigned to maintain and distribute this strain. This information is subject to change due to breeding, maintenance, and other actions. Please direct any questions on the information presented in this table to the MMRRC Distribution Center.

2 If an assessment has not been performed by the MMRRC (as indicated by "NO"), investigators may request specific testing for a fee. Requests should be submitted directly to the MMRRC Distribution Center assigned to the management, archiving, and distribution of the strain. A full listing of available testing and analytical services is available at https://www.mmrrc.org/about/services.php.

3 This information may or may not apply to each individual engineered allele (e.g., Cre, FlpO) present in the strain.

4 Recovery refers to thawing, in vitro fertilization (IVF), and/or embryo culture leading to live offspring.

Kmt2cem1Kaig
Name: lysine (K)-specific methyltransferase 2C; endonuclease-mediated mutation 1, Kai Ge
Synonyms: Mll3KI, MLL3 Y4792A
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 5
Alteration at locus: Knock-In
Kmt2dem1Kaig
Name: lysine (K)-specific methyltransferase 2D; endonuclease-mediated mutation 1, Kai Ge
Synonyms: Mll4KI, MLL4 Y5477A
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 15
Alteration at locus: Knock-In
Kmt2c
Name: lysine (K)-specific methyltransferase 2C
Synonyms: E330008K23Rik, HALR, Mll3
Type: Gene
Species: Mouse
Chromosome: 5
NCBI: 231051
Homologene: 46480
Kmt2d
Name: lysine (K)-specific methyltransferase 2D
Synonyms: C430014K11Rik, Mll4, Mll2, bapa
Type: Gene
Species: Mouse
Chromosome: 15
NCBI: 381022
HGNC: HGNC:7133
Homologene: 86893
Genetic Alterations
knock-in of Kmt2c (Mll3) and Kmt2d (Mll4) catalytically deficient alleles. The Mll3 allele contains a Y4792A (Tyr4792Ala) substitution, and the Mll4 allele contains a Y5477A (Tyr5477Ala) substitution. The point mutations were introduced by CRISPR/Cas9-mediated genome editing and eliminate the methyltransferase activities of MLL3 and MLL4 without constitutively deleting the proteins.
ES Cell Line
Not applicable
Phenotype
Homozygous Mll3 knock-in mice survive to adulthood, although at slightly reduced numbers, and are fertile. In contrast, homozygous Mll4 knock-in mice die around birth and exhibit defective saccular structures in the lung.

Complete homozygosity for both enzyme-dead alleles (Mll3KI/KI;Mll4KI/KI) results in early embryonic lethality. Double-homozygous embryos appear morphologically normal at E3.5 but develop severe abnormalities by E6.5–E7.5 and are found only as partially resorbed remnants by E8.5. These embryos exhibit defective anterior visceral endoderm migration and fail to express the primitive streak markers EOMES and T/BRACHYURY appropriately, indicating a failure to initiate gastrulation.

Mice heterozygous for both alleles are viable, survive to adulthood, are fertile, and do not display an overt phenotype compared to wild-type mice.
MeSH Terms
  • Animals
  • Mice
  • Cell Differentiation/genetics
  • Embryonic Development/genetics
  • Embryonic Stem Cells
  • Histone-Lysine N-Methyltransferase/genetics
Strain GQC Summary
Gene Specific Genotyping:

To request gene-specific and other genotyping services for a strain, please contact the distribution MMRRC Center for more information.

Background Genetic Quality:

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.

Suggested Control Mice
Littermates of all relevant genotypes.
  • Abnormal embryo development (MP:0001672)
  • Early Embryonic Development
  • Gastrulation
  • Abnormal gastrulation (MP:0001695)
  • Embryonic Lethality (MP:0008762)
  • Extraembryonic Tissue Development
  • Embryonic Stem Cell Biology and Differentiation
  • Abnormal cell differentiation (MP:0005076)
  • abnormal cell differentiation
  • Epigenetics / Chromatin Biology
  • Histone Methylation / H3K4 Methylation
  • Enhancer Regulation and Gene Expression
  • Cardiomyogenesis
  • abnormal heart morphology (MP:0000266)
  • Lung Development
  • abnormal lung morphology (MP:0001175)
Submitter
Kai Ge, Ph.D., National Institutes of Health (NIH).
Primary Reference

Xie G, Lee JE, Senft AD, Park YK, Jang Y, Chakraborty S, Thompson JJ, McKernan K, Liu C, Macfarlan TS, Rocha PP, Peng W, Ge K. MLL3/MLL4 methyltransferase activities control early embryonic development and embryonic stem cell differentiation in a lineage-selective manner. Nat Genet. 2023 Apr;55(4):693-705. doi: 10.1038/s41588-023-01356-4. Epub 2023 Apr 3. (Medline PMID: 37012455)

Strain Development
The Mll3 and Mll4 knock-in alleles were generated using CRISPR/Cas9-mediated genome editing. sgRNAs targeting genomic sequences near Mll3 Y4792 and Mll4 Y5477 were co-microinjected with the corresponding single-stranded donor oligonucleotides and Cas9 nickase mRNA into the cytoplasm of zygotes collected from B6D2F1/J females. Injected embryos were cultured overnight to the two-cell stage and transferred into the oviducts of pseudopregnant CD-1 surrogate females. Mosaic founders carrying the respective knock-in alleles were identified by PCR, and the Y4792A and Y5477A substitutions were confirmed by Sanger sequencing. Founder mice were subsequently crossed with wild-type C57BL/6J mice to establish germline transmission of the individual Mll3 and Mll4 knock-in alleles. Following germline transmission, mice heterozygous for the Mll3 and Mll4 knock-in alleles were bred to establish the individual lines. The two lines were subsequently crossed to generate Mll3KI/+;Mll4KI/+ double-heterozygous mice. Mice were subsequently crossed with wild-type C57BL/6J mice for at least 5 generations before experiments.

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.

Colony and Husbandry Information

For more information about this colony's health status contact csmmrrc@jax.org
Coat Color
Black
Eye
Black
MMRRC Breeding System
Random intra-strain mating
Generation
N5
Overall Breeding Performance
Good
Viability and Fertility: Female Male Comments
Homozygotes are viable: No No
Homozygotes are fertile: N/A N/A
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Greater than 12 months
Average litter size
7 to 9
Recommended wean age
3 Weeks
Average Pups Weaned
7 to 9

Order Information

Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at csmmrrc@jax.org for more details.

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

A Commercial License Agreement from the Submitter is required for for-profit entities to use this strain. For more information, please contact Mythreyi Shastri.

A Commercial License Agreement from the Submitter is required for for-profit entities to use this strain. For more information, please contact Mythreyi Shastri

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
076149-JAX-2-2-F
076149-JAX-2-2-M
076149-JAX-2-4-F
076149-JAX-2-4-M
076149-JAX-4-2-F
076149-JAX-4-2-M
Heterozygous for Kmt2cem1Kaig /eterozygous for Kmt2dem1Kaig
Heterozygous for Kmt2cem1Kaig / Heterozygous for Kmt2dem1Kaig
Heterozygous for Kmt2cem1Kaig / Wildtype for Kmt2dem1Kaig
Heterozygous for Kmt2cem1Kaig / Wildtype for Kmt2dem1Kaig
Wildtype for Kmt2cem1Kaig / Heterozygous for Kmt2dem1Kaig
Wildtype for Kmt2cem1Kaig / Heterozygous for Kmt2dem1Kaig
$236.00 / $236.00
Non-Profit / For-Profit
Per Mouse The csmmrrc@jax.org may assess additional fees for any special requests (e.g., specific age or weight of mice, etc.).
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

Some MMRRC strains were submitted by the submitter as cryopreserved germplasm, and because these strains were not cryopreserved by the MMRRC, we have not assessed the quality, nor genotype, of this material. Our expertise in reviving mice from various qualities of frozen sperm and embryos, using methods like IVF and ICSI, gives us confidence in successful recoveries in most cases. However, due to the uncertain quality of these samples, we'll limit revival attempts to two per order. Additional attempts are available for a fee, on top of standard charges, if requested. It's important to note that some strains may lack the expected mutation, so we can't assure successful order fulfillment until we attempt to revive the strain.

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.