B6.Cg-Kat6a^tm2.1Avo/TthoJ

Stock number: 039488
Product name: Moz^lox
Research areas: Cancer Research, Cardiovascular Research, Cell Biology Research, Developmental Biology Research, Hematological Research, Internal/Organ Research, Neurobiology Research, Research Tools

Description

Moz^lox mice have loxP sites flanking exons 3-7 of the Kat6a gene. These mice may be useful when studying the development of hematopoietic stem cells and the regulation of hematopoiesis as well as senescence and transcriptional regulation of embryonic development.

Detailed description

Moz^lox mice have loxP sites flanking exons 3-7 of K(lysine) acetyltransferase 6A (Kat6a) gene. Moz encodes a histone acetyltransferase that activates gene expression, especially at the Hox, Dlx and Tbx loci. KAT6A cooperatively promotes transcription of genes regulating hematopoiesis. It is a target of recurrent chromosomal translocations leading to acute myeloid leukemia. KAT6A fusion to the CREB binding protein results in acute myeloid leukemia (AML) with poor patient outcomes. Mutations in MOZ protein complex associated genes have been linked to the onset of intellectual disability and other neurological disorders.

Homozygous mice are viable and fertile. When bred to Mx1-cre transgenic mice (Stock No. 003556), deletion induced with poly(I:C) in the hematopoietic system results in efficient deletion of Moz in bone marrow. This causes a rapid loss of adult bone marrow HSCs, defined both by characteristic cell surface markers and also functionally through transplantation assays. Moz-deficient mice show a profound homeotic transformation of the axial skeleton. They have aortic arch and cardiac ventricular septal defects. Fibroblasts isolated from Moz null embryos rapidly become senescent. Bone marrow from Moz^fl/fl;Mx1-cre donor cells are unable to reconstitute the hematopoietic system of lethally irradiated recipients in the absence of competitor HSCs.

These mice may be useful when studying the development of hematopoietic stem cells and the regulation of hematopoiesis as well as senescence and transcriptional regulation of embryonic development.

The donating investigator has deposited a group of floxed strains that are useful for studying development of hematopoietic stem cells and the regulation of hematopoiesis:
Kat6a^fl [Moz3^lox] (Stock No. 039488)
Phf6^lox (Stock No. 039489)
Kat7^lox [Hbo1^lox] (Stock No. 039490)
Ing5^fl (Stock No. 039502)
Ing4^fl (Stock No. 039503)

Development

The Moz^lox targeting vector was designed to insert loxP sites flanking exons 3-7 of the K(lysine) acetyltransferase 6A (Kat6a) gene, together with a frt-flanked neomycin resistance (neo) cassette. The construct was electroporated into B6.Cg-Thy1^a-derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the chimeric mice were bred to ROSA26::FLPe mice (Stock No. 009086) to remove the neo cassette. Resulting Moz^lox offspring were bred to C57BL/6J mice (Stock No. 000664) for at least 10 generations by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Kat6a^tm2.1Avo
Name: targeted mutation 2.1, Anne K Voss
MGI accession ID: MGI:5636783
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Moz^fl; Moz^lox
Marker symbol: Kat6a
Marker name: K(lysine) acetyltransferase 6A
Marker synonyms: 9930021N24Rik; ARTHS; MOZ; MRD32; MYST3; MYST-3; RUNXBP2; ZC2HC6A; Zfp220; ZNF220
Chromosome: 8
Strain of origin: B6.Cg-Thy1^a
Molecular note: Exons 3 to 7 were flanked by loxP sites (after removal of an Frt-flanked "Pgk1-neomycinphotransferase" selection cassette).