ABSTRACT
Nitric oxide synthase has been shown to mediate streptozocin-induced diabetes and to act as an antimicrobial agent in murine macrophages. Using a cDNA probe for the inducible form of nitric oxide synthase (Nos2) isolated from murine macrophages we have determined that the gene maps within 1 cM of the nude mutation on mouse Chromosome 11. The position of Nos2 was also mapped relative to the markers 115, Evi2, Cchlbl (previously unmapped), and Gfap. This map location is discussed relative to map locations for disease susceptibility loci involved in mediating cutaneous leishmaniasis (ScII) and autoimmune type-I diabetes (Idd4).
Subject(s)
Chromosome Mapping , Macrophages/enzymology , Mice, Nude/genetics , Nitric Oxide Synthase/genetics , Animals , Crosses, Genetic , Diabetes Mellitus, Type 1/genetics , Enzyme Induction/genetics , Female , Genetic Linkage , Genetic Markers , Leishmaniasis, Cutaneous/genetics , Male , Mice , Mice, Inbred BALB C , Muridae , Nitric Oxide Synthase/biosynthesisABSTRACT
Plasmacytomas (PCTs) were induced in 47% of BALB/cAnPt mice by the intraperitoneal injection of pristane, in 2% of (BALB/c x DBA/2N)F1, and in 11% of 773 BALB/cAnPt x (BALB/cAnPt x DBA/2N)F1 N2 backcross mice. This result indicates a multigenic mode of inheritance for PCT susceptibility. To locate genes controlling this complex genetic trait, tumor susceptibility in backcross progeny generated from BALB/c and DBA/2N (resistant) mice was correlated with alleles of 83 marker loci. The genotypes of the PCT-susceptible progeny displayed an excess homozygosity for BALB/c alleles within a 32-centimorgan stretch of mouse chromosome 4 (> 95% probability of linkage) with minimal recombination (12%) near Gt10. Another susceptibility gene on mouse chromosome 1 may be linked to Fcgr2 (90% probability of linkage); there were excess heterozygotes for Fcgr2 among the susceptible progeny and excess homozygotes among the resistant progeny. Regions of mouse chromosomes 4 and 1 that are correlated with PCT susceptibility share extensive linkage homology with regions of human chromosome 1 that have been associated with cytogenetic abnormalities in multiple myeloma and lymphoid, breast, and endocrine tumors.
