Asxl1 Conditional Knockout mouse models

Additional sex combs like 1, encoded by Asxl1 and orthologous to human ASXL1, scaffolds the polycomb repressive deubiquitinase complex by binding BAP1 through its ASXM region and stimulating removal of H2AK119 ubiquitin, while its PHD finger and HARE-HTH module direct chromatin engagement. Myeloid disease alleles cluster as frameshift and nonsense events in the final exon, producing a truncated protein that escapes degradation and behaves as a gain of function, enhancing BAP1 catalysis, depleting H3K27 trimethylation, and derepressing posterior HOXA genes in myelodysplastic syndrome, chronic myelomonocytic leukemia, and secondary AML. Design follows that distinction: a conditional null reports haploinsufficiency and steady-state hematopoiesis, whereas a knockin encoding the truncated mutant recapitulates clonal expansion and transformation that nulls miss entirely. Asxl2 and Asxl3 provide partial buffering in some tissues, so compound genetics may be warranted. Pair inducible Mx1-Cre or Vav-Cre with transplantation readouts when scoring stem cell self-renewal.

A floxed Asxl1 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.