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Strain Name:
B6.Cg-Kmt2dtm2.1Kaig/Mmjax
Stock Number:
076150-JAX
Citation ID:
RRID:MMRRC_076150-JAX
Other Names:
MLL4SET-flox/flox

Strain Information

QUALITY CONTROL OF B6.Cg-Kmt2dtm2.1Kaig/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 distribution n.d.
Fecundity/breeding performance n.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.

Kmt2dtm2.1Kaig
Name: lysine (K)-specific methyltransferase 2D; targeted mutation 2.1, Kai Ge
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 15
Alteration at locus: Conditional
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
Loxp flanked exons 50 and 51 of the Kmt2d (Mll4) gene creating a conditional-ready allele.

ES Cell Line
v6.5 derived from (C57BL/6 x 129S4/SvJae)F1
Phenotype

Homozygous conditional ready mice are fertile and viable, exhibiting no overt phenotype.

Conditional phenotype: Upon Cre-mediated deletion of exons 50 and 51, the entire enzymatic SET domain of MLL4 is removed. When homozygous conditional mice were crossed with Myf5-Cre mice, the resulting Mll4SETf/f;Myf5-Cre mice survived until birth. E17.5–E18.5 mutant embryos were unable to breathe and died immediately after isolation. They displayed an abnormal hunched posture, impaired back muscles, altered brown adipose tissue morphology, and reduced muscle mass, although overall brown adipose tissue mass was similar to wild-type controls.

The relatively moderate adipose phenotype following MLL4 SET-domain deletion alone was attributed to possible compensation by MLL3. Simultaneous deletion of the MLL3 and MLL4 SET domains in Myf5-expressing progenitors resulted in a more severe phenotype characterized by profound reductions in brown adipose tissue and muscle mass and an inability to breathe at E18.5.

MeSH Terms
  • Adipogenesis/genetics
  • Adipose Tissue/growth & development
  • Adipose Tissue/metabolism
  • Animals
  • Enhancer Elements, Genetic
  • Histone-Lysine N-Methyltransferase/chemistry
  • Histone-Lysine N-Methyltransferase/metabolism
  • Histones/genetics
  • Histones/metabolism
  • Mice
  • Mice, Transgenic
  • Muscle Development
  • Mutation
  • Protein Domains
  • Protein Stability
  • Sequence Deletion
  • Thermogenesis
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.
  • Developmental Biology
  • Prenatal/perinatal lethality (MP:0002081)
  • Adipose Tissue Development
  • Abnormal adipose tissue morphology (MP:0000003)
  • Abnormal brown adipose tissue morphology (MP:0002971)
  • Adipogenesis
  • Abnormal adipocyte differentiation (MP:0011168)
  • Skeletal Muscle Development
  • Abnormal skeletal muscle morphology (MP:0000759)
  • Decreased skeletal muscle mass (MP:0004819)
  • Cell Differentiation
  • Abnormal cell differentiation (MP:0005076)
  • Epigenetics / Chromatin Biology
  • Histone H3K4 Methylation
  • Enhancer Regulation
  • MLL3/MLL4 Biology
  • Lipid Metabolism
  • Abnormal lipid metabolism (MP:0013245)
Submitter
Kai Ge, Ph.D., National Institutes of Health (NIH).
Primary Reference

Jang Y, Broun A, Wang C, Park YK, Zhuang L, Lee JE, Froimchuk E, Liu C, Ge K. H3.3K4M destabilizes enhancer H3K4 methyltransferases MLL3/MLL4 and impairs adipose tissue development. Nucleic Acids Res. 2019 Jan 25;47(2):607-620. doi: 10.1093/nar/gky982. (Medline PMID: 30335158)

Strain Development

The Kmt2d conditional line was generated by targeted modification of the endogenous Kmt2d (Mll4) locus. A targeting construct containing Mll4 exons 50 and 51 was designed with a single loxP site at the 5′ end of exon 50 and a loxP/FRT-flanked neomycin-resistance cassette at the 3′ end of exon 51. The linearized targeting construct was electroporated into wild-type v6.5 embryonic stem (ES) cells (derived from (C57BL/6 x 129S4/SvJae)F1). Following G418 selection, surviving ES cell clones were expanded and screened by PCR to identify correctly targeted ES cells which were subsequently microinjected into mouse blastocysts to generate chimeric mice. Mice demonstrating germline transmission of the mutant allele were crossed with FLP1 mice (RRID:IMSR_JAX:003946) to remove the FRT-flanked neomycin selection cassette and establish the Kmt2d conditional allele. The resulting conditional allele retains loxP sites flanking exons 50 and 51, permitting Cre-mediated deletion of the MLL4 SET domain.


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
N/A
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: 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
076150-JAX-HOM-F
076150-JAX-HOM-M
076150-JAX-HET-F
076150-JAX-HET-M
076150-JAX-WT-F
076150-JAX-WT-M
Homozygous Female
Homozygous Male
Heterozygous / Hemizygous Female
Heterozygous / Hemizygous Male
Wild Type Female
Wild Type Male
$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.