| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Recently, we identified a novel human protein, ankyrin-repeated protein with PEST and a proline-rich region (ARPP). ARPP is characterized structurally by the presence of four ankyrin-repeated domains in its central portion. The amino acid sequence of ARPP is highly homologous with that of cardiac restricted ankyrin-repeated protein (CARP ; 52%), which suggests that ARPP and CARP may be members of the same family.
CARP expression was reported to be confined to the heart but barely detectable in skeletal muscle. In contrast, we observed high expression levels of ARPP in skeletal muscle and heart. ARPP was found selectively expressed in type 1 myofibers of skeletal muscle and, therefore, ARPP-positive myofibers were arranged in a checkerboard-like pattern. Recently, we found that ARPP expression was up-regulated in experimentally denervated skeletal muscle. Furthermore, we also found that ARPP expression was induced in various muscle diseases. These findings lead us to speculate that ARPP may be induced in atrophic muscle fibers and may play important functional roles in them.
To elucidate the biological function of ARPP, we generated the ARPP gene-disrupted mice (ARPP-/-mice). Morphological analysis revealed that the developmental process of the ARPP-/-mice were almost normal after birth. Furthermore, we could not any differences between the ARPP+/+ mice and ARPP-/-mice in the expression patterns of the muscle-specific genes, distribution patterns of muscle fiber type, and morphologic phenotypes of muscles, suggesting that ARPP may not be essential for the development or morphogenesis of the skeletal muscle.
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