Immunohistochemical staining demonstrates markedly reduced myelination with dramatic improvement in brain myelination when hepatic arginase 1 expression is restored
Representative coronal images demonstrate myelination by MBP (brown) or its paucity at P14: (A) Arg1+/+, (B) Arg1−/−, (C) LNP A-formulated ARG1 mRNA Arg1−/−, and (D) LNP B-formulated ARG1 mRNA Arg1−/−. Representative images of myelination in the striatum (E) Arg1+/+, (F) Arg1−/−, (G) LNP A-formulated ARG1 mRNA Arg1−/−, and (H) LNP B-formulated ARG1 mRNA Arg1−/−. (E) Quantitation of the area fraction of MBP staining in the striatum per group. Representative images of myelination in the cingulum bundle (J) Arg1+/+, (K) Arg1−/−, (L) LNP A-formulated ARG1 mRNA Arg1−/−, and (M) LNP B-formulated ARG1 mRNA Arg1−/−. (N) Quantitation of the area fraction of MBP staining of the cingulum bundle per group (n = 5 per group). (In image A, the circle at lower left is bubble artifact.) ARG1, arginase 1; Arg1, arginase 1; P, postnatal; MBP, myelin basic protein; LNP, lipid nanoparticle; mRNA, messenger ribonucleic acid. Slides counterstained with hematoxylin. Data are presented as mean ± SD. (E–H) Bar, 200 μm; (J–M) bar, 100 μm.