B6(SJL)-Dot1l^{tm1c(KOMP)Wtsi}/SyjoJ

Stock number: 035909
Product name: Dot1l^F
Research areas: Developmental Biology Research, Research Tools

Description

Dot1l^F/F mice have loxP sites flanking exon 2 of the Dot1l gene, making them useful for studying embryonic development, prenatal hematopoiesis, leukemia, and T cell development and differentiation.

Detailed description

Dot1l^F/F mice have loxP sites flanking exon 2 of the DOT1-like, histone H3 methyltransferase (S. cerevisiae) (Dot1l) gene. Dot1l encodes an H3K79 methyltransferase associated with transcriptional activation in embryonic development, prenatal hematopoiesis, leukemia, and T cell development and differentiation. Mice that are homozygous for this Dot1l^F/F allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 2 deleted in the cre-expressing tissues.

Development

The L1L2_gtk cassette was inserted at a position on Chromosome 10 downstream of exon 1 of the DOT1-like, histone H3 methyltransferase (S. cerevisiae) (Dot1l) gene. The cassette is composed of an FRT-flanked β-galactosidase/neomycin resistance gene fusion (lacZ/neo), and a polyadenylation site (SV40 polyA). This was followed by loxP sites flanking exon 2. The mutation was generated in C57BL/6N derived JM8 embryonic stem (ES) cells, and correctly targeted ES cells were injected into blastocysts. The resulting chimeric mice were bred to ACTFLPe mice (Stock No. 005703) to remove the lacZ/neo cassette and then subsequently mice were bred together to remove the FLPe expressing transgene. These Dot1l^F/F mice were bred to and maintained on a C57BL/6 background. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Dot1l^{tm1c(KOMP)Wtsi}
Name: targeted mutation 1c, Wellcome Trust Sanger Institute
MGI accession ID: MGI:5925348
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Dot1l^fl
Marker symbol: Dot1l
Marker name: DOT1-like, histone H3 methyltransferase (S. cerevisiae)
Marker synonyms: DOT1; KMT4; mDot1; NDNS
Chromosome: 10
Strain of origin: C57BL/6N
Molecular note: The L1L2_gtk cassette was inserted at position 80599973 of Chromosome 10 upstream of the critical exon 2 (Build GRCm39). The cassette is composed of an FRT flanked lacZ/neomycin sequence followed by a loxP site. An additional loxP site is inserted downstream of exon 2 at position 80600773. Exon 2 is thus flanked by loxP sites. A "conditional ready" (floxed) allele was created by flp recombinase expression in mice carrying this allele to remove the lacZ sequence and neo selection cassette, leaving exon 2 flanked by loxP sites.