Total absence of dystrophin expression exacerbates ectopic myofiber calcification, fibrosis, and alters macrophage infiltration patterns.

Total absence of dystrophin expression exacerbates ectopic myofiber calcification, fibrosis, and alters macrophage infiltration patterns. Am J Pathol. 2019 Nov 11;: Authors: Young CN, Gosselin MR, Rumney R, Oksiejuk A, Chira N, Bozycki L, Matryba P, Łukasiewicz K, Kao AP, Dunlop J, Robson SC, Zabłocki K, Górecki DC Abstract Duchenne muscular dystrophy (DMD) causes severe disability and death of young men due to progressive muscle degeneration aggravated by sterile inflammation. DMD is also associated with cognitive and bone-function impairments. This complex phenotype results from the cumulative loss of a spectrum of dystrophin isoforms expressed from the largest human gene. Although there is evidence for the loss of shorter isoforms having impact in the central nervous system, their role in muscle is unclear. We found that at eight weeks, the active phase of pathology in dystrophic mice, dystrophin-null mice (mdxβgeo) presented with a mildly exacerbated phenotype but without an earlier onset, increased serum CK levels, or decreased muscle strength. However, at 12 months, mdxβgeo diaphragm strength was lower while fibrosis increased, compared to mdx. The most striking features of the dystrophin-null phenotype were increased ectopic myofiber calcification and altered macrophage infiltration patterns, particularly the close association of macrophages with calcified fibers. Ectopic calcification had the same temporal pattern of pre...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research