Mll4f/f mice possess loxP sites flanking exons 16-19 of the lysine (K)-specific methyltransferase 2D (Kmt2d) gene. These floxed mice are useful for tissue specific deletion of Kmt2d when studying the role of histone H3 lysine 4 di-methylation in development and the onset of certain cancers.
Kai Ge, National Institutes of Health, NIH
Mll4f/f mice possess loxP sites flanking exons 16-19 of the lysine (K)-specific methyltransferase 2D (Kmt2d) gene. KMT2D is widely expressed in adult tissues and is essential for in regulating development, differentiation, metabolism, and tumor suppression. Mutations in KMT2D are associated with developmental diseases such as Kabuki syndrome and congenital heart disease, and various forms of cancer. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 16-19 deleted in the cre-expressing tissues. Removal of the floxed exons causes an open reading frame shift and creates a stop codon in exon 20, which leads to the creation of a truncated MLL4 protein lacking the C-terminal ~4200aa.
Homozygous mice are viable and fertile. In 2019, colonists at The Jackson Laboratory found that pups from homozygous matings are severely runted. The donating investigator reports that this may be due to a decrease in Kmt2d gene expression caused by the insertion of loxP sites. When maintaining a live colony, heterozygous mice may be bred together to produce healthy homozygous offspring. Alternatively, heterozygous females can be bred to homozygous males. It is unknown at this time if offspring from homozygous females bred to heterozygous males are runted.
The Mll4f targeting vector was designed to insert a loxP site upstream of exon 16, and a frt-flanked neomycin selection cassette, followed by a second loxP site, downstream of exon 19 of the lysine (K)-specific methyltransferase 2D (Kmt2d) gene. The construct was electroporated into embryonic stem (ES) cells. Resulting ES cells were injected into blastocysts and resulting Mll4floxneo/+ males were bred to C57BL/6J females. Subsequently, mice were bred to ROSA26::FLPe mice (Stock No. 003946) to remove the neo cassette. Progeny were crossed to remove the Flp-expressing transgene, and offspring were bred to C57BL/6J mice by the donating lab (see SNP note below). Frozen sperm were shipped to The Jackson Laboratory Repository. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Twelve of the 43 markers throughout the genome were segregating, suggesting an incomplete backcross.
|Allele Name||targeted mutation 1.1, Kai Ge|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||Kmt2dtm1.1Kaig; targeted mutation 1.1, Kai Ge|
|Gene Symbol and Name||Kmt2d, lysine (K)-specific methyltransferase 2D|
|Gene Synonym(s)||Mll2; BC032281; CAGL114; cDNA sequence BC032281; KMS; TNRC21; MLL2; MLL4; ALR; KABUK1; myeloid/lymphoid or mixed-lineage leukemia 2; AAD10; cDNA sequence BC058659; BC058659; C430014K11Rik; C430014K11Rik; RIKEN cDNA C430014K11 gene; Mll2; Mll4|
|Strain of Origin||Not Specified|
|Molecular Note||A loxP site was inserted upstream of exon 16. An FRT-flanked neomycin resistance cassette with a 3 loxP site was inserted downstream of exon 19. Flp-mediated recombination removed the selection cassette and left exons 16 through 19 floxed.|
Homozygous mice are viable and fertile. In 2019, colonists at The Jackson Laboratory found that pups from homozygous matings are severely runted. When maintaining a live colony, heterozygous mice may be bred together to produce healthy homozygous offspring. Alternatively, heterozygous females can be bred to homozygous males. It is unknown at this time if offspring from homozygous females bred to heterozygous males are runted.
When using the Mll4f mouse strain in a publication, please cite the originating article(s) and include JAX stock #032152 in your Materials and Methods section.
|Heterozygous or wildtype for Kmt2d<tm1.1Kaig>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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