Hat1flox mutant mice possess loxP sites flanking exon 3 of the targeted gene. HAT1 is involved in the rapid acetylation of newly synthesized soluble cytoplasmic histones. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 3 deleted in cre-expressing tissues.
For example, when crossed to a strain with widespread Cre recombinase expression, HAT1 deficient mice exhibit neonatal lethality due to mesenchymal cell hyperproliferation in the lung. Mice also have craniofacial defects, including nasal cavity defects and defects or absence of the lower jaw bone. Mouse embryonic fibroblasts derived from Hat1 KO mice are sensitive to DNA damaging agents and display a high level of genome instability.
A targeting vector was designed to insert loxP site upstream of exon 3, and a frt-flanked neomycin resistance (neo) cassette followed by a single loxP site downstream of exon 3 of the histone aminotransferase 1 (Hat1) gene. The construct was electroporated into B6.Cg-Thy1a-derived Bruce 4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric mice were bred with C57BL/6J mice. The donating investigator reported that mice were bred to C57BL/6J mice for at least 10 generations (see SNP note below). Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 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. Five of the 27 markers throughout the genome were segregating from an undisclosed source, suggesting a genetic contamination and incomplete backcross.
|Allele Name||targeted mutation 1, Mark R Parthun|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Hat1, histone aminotransferase 1|
|Strain of Origin||B6.Cg-Thy1a|
|Molecular Note||A targeting vector was designed to insert loxP site upstream of exon 3, and a frt-flanked neomycin resistance (neo) cassette followed by a single loxP site downstream of exon 3.|
When maintaining a live colony, mice homozygous for the floxed allele may be bred together.
When using the Hat1