Bix described Mina as a molecular handle scientists can use to grasp the rest of the new pathway, whose other elements Bix described as links in a chain. "Each one of those links, including the gene we discovered, constitutes a novel target for therapeutic interventions that could help either promote or diminish development toward the Th2 fate," he explained.

In this study, Bix and his colleagues also proposed a reason for the wide variation in Th2 bias between different mouse strains. The researchers pointed to a region of DNA that included the Mina promoter. They decoded the same region in five different mouse strains. Two favored Th2 production and three did not. The scientists eventually linked the differences to 21 single nucleotide polymorphisms (SNPs). SNPs are relatively common variations in the makeup of particular genes. Those SNPs distinguished mice with high numbers of Th2 cells from those with less Th2 bias. The researchers noted the same DNA region might contain other genomic variations that explain differences in Mina activity.

Mina belongs to a particular family of genes known as transcription factors. Cells use transcription factors to help carry out the instructions genes carry. Mina first surfaced in 2002 in connection with human cancer. Those earlier studies suggested Mina was a target of the Myc oncogene, or cancer gene. However, in T helper cells, Bix's group found no evidence linking Mina expression with Myc activity.

Other questions remain. Mina lacks an obvious location for binding to the IL-4 promoter. Researchers believe another transcription factor, named NFAT, plays a role in the hookup. They noted the Dice1.2 region of chromosome 16 where Mina was found might contain other genes that contribute to Th2 balance. Mina's role in response to a Leishmania major infection also remains unclear. Earlier research linked response to the infection to the same DNA region where Mina was found. Researchers speculated Mina might also be the foundation of that response.

SOURCE St. Jude Children's Research Hospital

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