Dual transgene amelioration of Lama2-null muscular dystrophy.

ABSTRACT: Null mutations of the Lama2-gene cause a severe congenital muscular dystrophy and associated neuropathy. In the absence of laminin-α2 (Lmα2) there is a compensatory replacement by Lmα4, a subunit that lacks the polymerization and α-dystroglycan (αDG)-binding properties of Lmα2. The dystrophic phenotype in the dy^3K/dy^3K Lama2^-/- mouse were evaluated with transgenes driving expression of two synthetic laminin-binding linker proteins. Transgenic muscle-specific expression of αLNNd, a chimeric protein that enables α4-laminin polymerization, and miniagrin (mag), a protein that increases laminin binding to the receptor αDG, separately improved median mouse survival two-fold. The double transgenes (DT) improved mean survival three-fold with increases in overall bo

SUBMITTER: McKee KK 

PROVIDER: S-EPMC10771811 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature