Cloning of the murine non-muscle myosin heavy chain IIA gene ortholog of human MYH9 responsible for May-Hegglin, Sebastian, Fechtner, and Epstein syndromes

Abstract

Mutations in the non-muscle myosin heavy chain IIA gene ( MYH9) are responsible for May-Hegglin anomaly, Sebastian, Fechtner and Epstein syndromes. These ‘ MYH9-related’ diseases are inherited as an autosomal dominant trait and are characterized by a variable expressivity of clinical features, including macrothrombocytopenia, deafness, nephrites, cataract, and Döhle-like leukocyte inclusions. To gain information of the function of the non-muscle myosin heavy chain IIA protein (NMMHC-IIA), we have identified the murine orthologue Myh9 gene. The gene is localized in a region of chromosome 15 and encodes a predicted protein of 1960 amino acids. This protein shows a high homology to the human NMMHC-IIA with 98% identity. The Myh9 exon-intron junctions were deduced from a murine genomic clone that revealed a perfect conservation of the exon structure between the human and mouse gene. Myh9 is expressed in liver, kidney, lung, and spleen. A low level of transcripts was detected also in heart and brain while no expression was revealed in skeletal muscle and testis. In vertebrates, NMMHC-IIA shows a striking degree of homology to NMMHC-IIB, which is expressed at higher level in mouse brain and testis than in other tissues, confirming the hypothesis that the two non-muscle myosins have different functional roles within cells.