U2af1 Conditional Knockout mouse models

Recognition of the 3 prime splice site depends on U2af1, the mouse ortholog of human U2AF1, the small subunit of the U2 auxiliary factor heterodimer, which uses two CCCH zinc fingers to contact the invariant AG dinucleotide and flanking nucleotides while its U2AF homology motif binds U2AF2 and licenses U2 snRNP loading at the branch point. Myeloid disease mutations are heterozygous and mutually exclusive with SF3B1 and SRSF2 lesions, with S34F and S34Y altering preference at the position three nucleotides upstream of the AG and Q157P or Q157R altering the position immediately downstream, producing distinct cassette exon and intron retention programs rather than global splicing failure; identical substitutions recur in lung adenocarcinoma. Because complete loss is not tolerated, the correct design is a conditional or doxycycline-inducible heterozygous hotspot knockin at the endogenous locus, induced with Mx1-cre or Vav1-cre to capture dysplastic hematopoiesis. Match allele to endpoint, whether isoform mapping, competitive repopulation, or spliceosome modulator sensitivity.

A floxed U2af1 allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.