Evolutionarily conserved clusters of colon with lung cancer susceptibility loci, linked with most DUSP phosphatase genes, may help to dissect mechanisms of cancer susceptibility

We show evolutionarily conserved pairwise genetic linkage and clustering of majority of colon and lung cancer susceptibility QTLs in mice, rats and humans. The patterns of susceptibility or resistance to these two cancers in recombinant congenic mouse strains were concordant and the responsible susceptibility loci closely linked, in spite of completely different carcinogens and protocols used for induction of the two tumors. Most DUSP (Dual specificity phosphatase) genes are linked to these clusters. These data suggest that an important part of colon and lung cancer susceptibility is controlled by related and evolutionarily conserved processes.

Edward Arthur Boyse. 11 August 1923—14 July 2007

Edward Boyse was the consummate scientist. His interest was piqued by the unique, the undeveloped and the unthought of. When an area of study gained widespread attention, he moved on. The development of the field of cell surface immunogenetics, of which he was master, relied heavily on the use of Boyse's congenic mouse strains, and on his improved methods for reliable serology. He founded the new discipline of odourtype genetics, revealing how immunohaplotypes were involved in assortative mating and related behaviours, thus promoting heterozygosity. He pioneered the now crowded field of cord-blood cryopreservation and transplantation, conducting the first laboratory studies in mice and assembling the clinical team that performed the first human cord-blood transplant. An educator and protector of graduate students, he instilled rigorous scientific discipline while broadening horizons. Boyse was a pilot in World War II, a physician, a biomedical innovator and a demon squash player. A lover of classical music (which love he transmitted to his children) and the Beatles (love of which they transmitted to him), he strenuously avoided both the intellectually self-absorbed and the ostentatiously populist. In leisure, he flew, hiked, ran, biked and, periodically, upholstered. Wit, generosity and loyalty were the most prominent features of his unique personality.

A novel isoform of the Ly108 gene ameliorates murine lupus

Studies of human systemic lupus erythematosus patients and of murine congenic mouse strains associate genes in a DNA segment on chromosome 1 with a genetic predisposition for this disease. The systematic analysis of lupus-prone congenic mouse strains suggests a role for two isoforms of the Ly108 receptor in the pathogenesis of the disease. In this study, we demonstrate that Ly108 is involved in the pathogenesis of lupus-related autoimmunity in mice. More importantly, we identified a third protein isoform, Ly108-H1, which is absent in two lupus-prone congenic animals. Introduction of an Ly108-H1–expressing transgene markedly diminishes T cell–dependent autoimmunity in congenic B6.Sle1b mice. Thus, an immune response–suppressing isoform of Ly108 can regulate the pathogenesis of lupus.