New immunodeficient mouse strains bred by introducing beige and xid mutations into the KSN nude strain.

We introduced two mutant genes (beige or bg, which induces a deficiency of natural killer activity, and xid, which decreases the production of immunoglobulins) into KSN nude mice with high reproductive performance. At first we produced the KSN-bg/bg(nu/nu) (KSN-bg) and KSN-xid/xid(nu/nu) (KSN-xid) congenic strain by backcross (cross-intercross method). After we identified homozygosity at the biochemical locus and polymorphic microsatellite loci, we mated KSN-bg and KSN-xid mice, and selected the KSN-xid/xid;bg/bg(nu/nu) (KSN-BNX) mice from the progeny. Furthermore we introduced the non-nude gene, which originated from CBA/N, into the KSN strain and produced KSN-nu/+ (KS) mice that have the same genetic background except for the nu locus. All strains had as high a reproductivity rate as the parental KSN mice. The KSN-xid and KSN-BNX mice had a reduced percentage of B220-positive cells in the spleen compared with KSN and KSN-bg mice, but they had increased percentages of Thy-1 and asialo GM1-positive cells. The serum immunoglobulin concentrations of BNX were as low as those of KSN-xid mice. Both KSN-bg and KSN-BNX mice had deficient natural killer activity in the spleen, whereas KSN-xid mice had increased natural killer activity. Compared with nude mice, the growth of the human thyroid tumor cell line transplanted subcutaneously was enhanced in BNX mice. These KSN, KSN-bg, KSN-xid, KSN-BNX, and KS nice not only are of value for use in various fields as the hosts of xenograft but also are good models of the combination effect of multiple immunodeficient genes.