IL-15 is a member of the IL-2 family of cytokines that stimulates proliferation of activated T cells, NK cells, and B cells through a receptor complex containing a high affinity ligand binding subunit, IL-15Ra and the Jak/STAT signaling elements IL-2Rb and g c. In addition IL-15 stimulates cytolytic effector function and facilitates the survival of CD8 memory T cells. IL-15 deficient mice lack natural killer (NK) cells and have marked reductions in memory CD8 T cells, NK1.1 T cells, and Thy1- CD8a intraepithelial lymphocytes (IELs). These mice are unable to mount a protective immune response to challenge with vaccinia virus. They should be useful for exploring the role of IL-15 in other host immune responses.
Genetic Background: C57BL/6 Background
Origin: C57BL/6 mice deficient in IL15 were generated by gene targeting in the laboratory of Dr. Jacques Peschon of the Immunex Corporation in 1996. The IL15 gene was disrupted by replacing a 7.5 kb fragment containing IL15 exons 3-5 with a PGK-neo cassette. The disrupted gene was introduced into ES cells of C57BL/6 origin developed at Immunex and injected into BALB/c blastocysts to create chimeric mice. Resulting male chimeric animals were bred to C57BL/6 females and offspring heterozygous for the IL15 knockout allele were crossed to generate IL15 deficient mice (IL15-/-). Different C57BL/6 sublines were used during the development of this line and therefore an exact control mouse was not available. However, C57BL/6NTac mice were used as controls in the original studies. Recently we completed backcrossing these mice an additional 5 times onto C57BL/6NTac mice and intracrossed them to make them homozygous for the IL15 knockout allele. We now consider the Taconic B6 (C57BL/6NTac) mouse to be a more appropriate control for line 4269.
Kennedy MK, Glaccum M, Brown SN, Butz EA, Viney JL, Embers M, Matsuki N, Charrier K, Sedger L, Willis CR, Brasel K, Morrissey PJ, Stocking K, Schuh JCL, Joyce S and Peschon JJ. 2000. Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med. 2000 Mar 6;191(5):771-80