A new allele of Lyl1 confirms its important role in hematopoietic stem cell function

Lyl1 codes for a bHLH protein that is an important regulator of hematopoietic stem cell function. An existing mutant allele of Lyl1 features a lacZ gene inserted in-frame into the fourth exon, leaving behind the N-terminus and the DNA-binding basic region, resulting in a translated chimeric protein. Here, we have generated a null allele, which allowed us to examine residual function of the N-terminus in the absence of a bHLH region. The new Lyl1-/- mouse model exhibited a reduced ability to generate lymphoid lineages and a somewhat more severe hematopoietic repopulation defect when transplanting purified hematopoietic stem cells. Our data show that in the absence of the HLH but presence of the N-terminus, residual function of the Lyl1 is detectable but relatively minor. The new model may be of use for studies of Lyl1 in which a null allele is required, or for which presence of the LacZ may complicate the combined use of additional mouse models bearing the lacZ marker.