Hhex is a gene linked to blood cancers such as T-cell and early T-cell precursor acute lymphoblastic leukemia, a treatment-resistant subtype. An Hhex knockout mouse model would be invaluable for understanding the genetic basis of T-cell leukemias and finding possible treatments. However, Hhex is critical for embryonic development and conventional Hhex knockout mice do not survive past birth.
Reporting in the journal Stem Cells, Charnise Goodings, Ph.D., Utpal Davé, M.D., and colleagues have induced a conditional knockout of Hhex using vav-Cre transgenic mice. These Hhex conditional knockout mice are normal at birth and allow study of Hhex’s effect on adult blood cell production (hematopoiesis).
They found that Hhex is critical for adult hematopoietic stem and progenitor cell differentiation at different stages. Their study suggests Hhex is required for B-cell and early T-cell development, and for maintaining normal stem and progenitor cell populations. This mouse model has provided new insights into the normal function of Hhex in adult hematopoiesis and how its overexpression leads to T-cell leukemias.
The research was supported in part by the American Society of Hematology and the Department of Veterans Affairs and in part by National Institutes of Health grants GM062459, CA009592 and HL117624.
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