The lysine (K)-specific methyltransferase 2C (Kmt2c) and lysine (K)-specific methyltransferase 2D (Kmt2d) genes encode histone modification enzymes involved in regulating gene expression in early development, hematopoiesis, and neural function. Mutant KMT2C and KMT2D proteins, also referred to as MLL3 and MLL4, respectively, have been associated with developmental diseases such as Kabuki syndrome and congenital heart disease, and various forms of cancer. These Kmt2cf; Kmt2dAID; Cre-ER mice harbor a floxed Kmtc2 allele, a Cre/ERT2 fusion protein expressed from the Gt(ROSA)26Sor locus, and an AID-tagged Kmt2d allele. Mice homozygous for all three (3) alleles are viable and fertile with no overt phenotype. After tamoxifen-induced Cre-mediated recombination, the resulting offspring will have Kmtc2 exons 57-58 deleted in the cre-expressing tissues, resulting in the complete loss of KMT2C protein. These mice also express an AID-tagged Kmt2d allele, in which an AID tag was inserted immediately upstream of the Kmt2d start codon. When combined with a mouse line, or viral vector, that expresses the Japanese rice Oryza sativa F-box transport inhibitor response 1 (TIR1, formal name LOC4337827) protein, harboring the F74G modification, the resulting progeny will demonstrate rapid and reversible degradation of KMT2D-AID tagged protein, after exposure to the auxin derivative 5-phenyl-indole-3-acetic acid (5-Ph-IAA). The donating laboratory isolated primary preadipocytes from these mice and exposed the cells to tamoxifen, the resulting Cre-recombined Kmt2c null; Kmt2dAID cells were then infected with retroviruses expressing Oryza sativa TIR1, harboring the F74G modification. Depletion of KMT2D in the cells occurred within 2hours after treatment with 5-Ph-IAA. These Kmt2cf; Kmt2dAID; Cre-ER mice may be useful for studying the roles of KMT2C and KMT2D protein in cell differentiation and organogenesis, as well as in numerous cancers. Of note, the donating laboratory has also made the Kmt2dAID mouse line available as <a href="https://www.jax.org/strain/041109">RRID:MMRRC_075966-JAX</a>.

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Kmt2cf; Kmt2dAID; Cre-ER mice have an AID-tagged Kmt2d allele on a Cre-inducible Kmt2c knock-out background. These mice may be used in the second-generation auxin-inducible degron (AID2) system. When combined with an OsTir1-F74G-expressing mouse line or viral vector, the resulting progeny will demonstrate rapid and reversible degradation of KMT2D-AID tagged protein after exposure to the auxin derivative 5-Ph-IAA. Of note, the donating laboratory has also made the Kmt2dAID mouse line available as <a href="https://www.jax.org/strain/041109">RRID:MMRRC_075966-JAX</a>.

This strain is hosted by NIH's MMRRC, which partners with JAX for the distribution of this and other strains. For additional information and to purchase, please visit the MMRRC site.