Journal article

The Rothmund-Thomson syndrome helicase RECQL4 is essential for hematopoiesis

Monique F Smeets, Elisabetta DeLuca, Meaghan Wall, Julie M Quach, Alistair M Chalk, Andrew J Deans, Joerg Heierhorst, Louise E Purton, David J Izon, Carl R Walkley



Mutations within the gene encoding the DNA helicase RECQL4 underlie the autosomal recessive cancer-predisposition disorder Rothmund-Thomson syndrome, though it is unclear how these mutations lead to disease. Here, we demonstrated that somatic deletion of Recql4 causes a rapid bone marrow failure in mice that involves cells from across the myeloid, lymphoid, and, most profoundly, erythroid lineages. Apoptosis was markedly elevated in multipotent progenitors lacking RECQL4 compared with WT cells. While the stem cell compartment was relatively spared in RECQL4-deficent mice, HSCs from these animals were not transplantable and even selected against. The requirement for RECQL4 was intrinsic in he..

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Funding Acknowledgements

The authors would like to thank V. Sankaran, R. Dickins, and S. Lane for comments and discussion; S. Dewamitta and B. Liddicoat for technical assistance; and the SVH BioResources Centre for care of experimental animals. This work was supported by grants from the Leukaemia Foundation (to C.R. Walkley); a National Health and Medical Research Council (NHMRC) project grant (to C.R. Walkley); an NHMRC Career Development Award (to C.R. Walkley); an NHMRC Senior Research Fellowship (to J. Heierhorst and L.E. Purton); a Victorian Cancer Agency Clinical Research Fellowship (to M. Wall); and in part by the Victorian State Government Operational Infrastructure Support Program (to St. Vincent's Institute). C.R. Walkley is the Phillip Desbrow Senior Research Fellow of the Leukaemia Foundation.