Genetic Structure and Chromosomal Mapping of MyD88

Abstract

The myeloid differentiation (MyD) markerMyD88was initially characterized as a primary response gene, upregulated in mouse M1 myeloleukemic cells in response to differentiation induced by interleukin-6. Subsequent analysis revealed thatMyD88possesses a unique modular structure, which consists of an N-terminal “death domain,” similar to the intracellular segments of TNF receptor 1 and Fas, and a C-terminal region related to the cytoplasmic domains of theDrosophilamorphogen Toll and vertebrate interleukin-1 receptors. In this report we describe the cloning and gene structure of mouseMyD88.The complete coding sequence of mouseMyD88spans five exons, with the first exon encoding the complete death domain. Zooblot analysis revealed thatMyD88is an evolutionarily conserved gene.MyD88was localized to the distal region of mouse chromosome 9 by interspecific backcross mapping. The human homolog (hMyD88) was mapped to chromosome 3p22–p21.3 by PCR analysis of a human chromosome 3 somatic cell hybrid mapping panel. Northern blot analysis revealed widespread expression ofMyD88in many adult mouse tissues, and RT-PCR studies detectedMyD88mRNA in T and B cell lines and differentiating embryonic stem cells. The broad expression pattern demonstrates that mouseMyD88expression is not restricted to cells of myeloid lineage as was originally believed.