{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:00:47Z","timestamp":1791165647403,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1993,7,15]]},"abstract":"<jats:p>Murine mucopolysaccharidosis type VII is a heritable disease caused by a spontaneous mutation, gus(mps), closely linked to the beta-glucuronidase structural gene on chromosome 5. Mice homozygous for the mutation have a &gt; 200-fold decrease in beta-glucuronidase mRNA levels and virtually no enzyme activity detectable by a sensitive fluorometric assay. Approximately 20 kb of genomic DNA containing the beta-glucuronidase gene Gus and &gt; 2 kb of 5' and 3' flanking sequences were cloned from both a gus(mps)\/gus(mps) mouse and a +\/+ mouse of the progenitor strain. Restriction enzyme digests containing DNA fragments 20-400 bp in length were generated from each of the two Gus alleles and then compared by using nondenaturing polyacrylamide DNA-sequencing gels. This method rapidly identified a large number of restriction sites and was sensitive enough to detect a restriction fragment length variation resulting from a 1-bp deletion in the gus(mps) allele. DNA-sequence analysis of the mutant genomic fragment showed that the 1-bp deletion created a frameshift mutation within exon 10. Insertion of the deleted nucleotide by oligonucleotide site-directed mutagenesis restored function to the corrected mutant gene when transfected into gus(mps)\/gus(mps) fibroblasts. We concluded that the frameshift mutation, which introduces a premature stop codon at codon 497 in exon 10, accounts for the molecular, biochemical, and pathological abnormalities associated with the gus(mps) phenotype.<\/jats:p>","DOI":"10.1073\/pnas.90.14.6567","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:27:18Z","timestamp":1149064038000},"page":"6567-6571","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":102,"title":["A single-base-pair deletion in the beta-glucuronidase gene accounts for the phenotype of murine mucopolysaccharidosis type VII."],"prefix":"10.1073","volume":"90","author":[{"given":"M S","family":"Sands","sequence":"first","affiliation":[{"name":"Jackson Laboratory, Bar Harbor, ME 04609."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E H","family":"Birkenmeier","sequence":"additional","affiliation":[{"name":"Jackson Laboratory, Bar Harbor, ME 04609."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1993,7,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.90.14.6567","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:32:42Z","timestamp":1649856762000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.90.14.6567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,7,15]]},"references-count":0,"journal-issue":{"issue":"14","published-print":{"date-parts":[[1993,7,15]]}},"alternative-id":["10.1073\/pnas.90.14.6567"],"URL":"https:\/\/doi.org\/10.1073\/pnas.90.14.6567","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,7,15]]},"assertion":[{"value":"1993-07-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}