NF-kappa B-inducing kinase (NIK) plays critical roles in the development of lymph nodes and Peyer's patches, and microarchitecture of the thymus and spleen via NF-kappa B activation. Alymphoplasia (aly/aly) mice have a point mutation in the NIK gene that causes a defect in the activation of an NF-kappa B member ReIB. Here, we developed a novel method to determine the aly mutation by genetic typing using PCR. This method facilitated the easy establishment of a congeneic aly/aly mouse line. Indeed, we generated a mouse line with aly mutation on a BALB/cA background (BALB/cA-aly/aly). BALB/cA-aly/aly mice showed significant splenomegaly with extramedullary hemopoiesis, which was not significant in aly/aly mice on a C57BL/6 background. Interestingly, the splenomegaly and extramedullary hemopoiesis caused by the aly mutation was gender-dependent. These data together with previous reports on extramedullary hemopoiesis in ReIB-deficient mice suggest that NIK-ReIB signaling may be involved in the suppression of extramedullary hemopoiesis in adult mice. (C) 2011 Elsevier Inc. All rights reserved.