Nbn-Mre11 interaction is required for tumor suppression and genomic integrity.

ABSTRACT: We derived a mouse model in which a mutant form of Nbn/Nbs1^mid8 (hereafter Nbn^mid8) exhibits severely impaired binding to the Mre11-Rad50 core of the Mre11 complex. The Nbn ^mid8 allele was expressed exclusively in hematopoietic lineages (in Nbn ^-/mid8vav mice). Unlike Nbn ^flox/floxvav mice with Nbn deficiency in the bone marrow, Nbn ^-/mid8vav mice were viable. Nbn ^-/mid8vav mice hematopoiesis was profoundly defective, exhibiting reduced cellularity of thymus and bone marrow, and stage-specific blockage of B cell development. Within 6 mo, Nbn ^-/mid8 mice developed highly penetrant T cell leukemias. Nbn ^-/mi

SUBMITTER: Kim JH 

PROVIDER: S-EPMC6660787 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature