{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:31:24Z","timestamp":1790631084289,"version":"4.1.0"},"reference-count":51,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-DK36425"],"award-info":[{"award-number":["R01-DK36425"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Santhera Pharmaceuticals","award":["no number"],"award-info":[{"award-number":["no number"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,8]]},"abstract":"<jats:p>\n                    LAMA2 deficiency, resulting from a defective or absent laminin \u03b12 subunit, is a common cause of congenital muscular dystrophy. It is characterized by muscle weakness from myofiber degeneration and neuropathy from Schwann cell amyelination. Previously it was shown that transgenic muscle-specific expression of \u03b1LNNd, a laminin \u03b31\u2013binding linker protein that enables polymerization in defective laminins, selectively ameliorates the muscle abnormality in mouse disease models. Here, adeno-associated virus was used to deliver linker mini-genes to dystrophic\n                    <jats:italic>\n                      dy\n                      <jats:sup>2J<\/jats:sup>\n                      \/dy\n                      <jats:sup>2J<\/jats:sup>\n                    <\/jats:italic>\n                    mice for expression of \u03b1LNNd in muscle, or \u03b1LNNd\u0394G2\u2032, a shortened linker, in muscle, nerve, and other tissues. Linker and laminin \u03b12 levels were higher in \u03b1LNNd\u0394G2\u2032-treated mice. Both \u03b1LNNd- and \u03b1LNNd\u0394G2\u2032-treated mice exhibited increased forelimb grip strength. Further, \u03b1LNNd\u0394G2\u2032-treated mice achieved hind limb and all-limb grip strength levels approaching those of WT mice as well as ablation of hind limb paresis and contractures. This was accompanied by restoration of sciatic nerve axonal envelopment and myelination. Improvement of muscle histology was evident in the muscle-specific \u03b1LNNd-expressing mice but more extensive in the \u03b1LNNd\u0394G2\u2032-expressing mice. The results reveal that an \u03b1LN linker mini-gene, driven by a ubiquitous promoter, is superior to muscle-specific delivery because of its higher expression that extends to the peripheral nerve. These studies support a potentially novel approach of somatic gene therapy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.158397","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T12:00:33Z","timestamp":1653998433000},"source":"Crossref","is-referenced-by-count":24,"title":["Amelioration of muscle and nerve pathology of Lama2-related dystrophy by AAV9-laminin-\u03b1LN linker protein"],"prefix":"10.1172","volume":"7","author":[{"given":"Karen K.","family":"McKee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0387-2317","authenticated-orcid":true,"given":"Peter 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