Deficient T cell fate specification in mice with an induced inactivation of Notch1

Notch proteins are cell surface receptors that mediate developmental cell s pecification events. To explore the function of murine Notch1, an essential portion of the gene was flanked with loxP sites and inactivation induced v ia interferon-regulated Cre recombinase. Mice with a neonatally induced los s of Notch1 function were transiently growth retarded and had a severe defi ciency in thymocyte development. Competitive repopulation of lethally irrad iated wild-type hosts with wild-type- and Notch-1-deficient bone marrow rev ealed a cell autonomous blockage in T cell development at an early stage, b efore expression of T cell lineage markers. Notch1-deficient bone marrow di d, however, contribute normally to all other hematopoietic lineages. These findings suggest that Notch1 plays an obligatory and selective role in T ce ll lineage induction.