{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T08:51:32Z","timestamp":1773996692339,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,6,9]],"date-time":"2005-06-09T00:00:00Z","timestamp":1118275200000},"content-version":"vor","delay-in-days":3657,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[1995,6,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The <jats:italic>mnd<\/jats:italic> mouse shows a spontaneous adultonset hereditary neurological disease, with motor abnormality by 6 months of age, progressing to severe spastic paralysis and premature death. The disease is autosomal recessive, with heterozygote effects seen under stress. It maps to mouse chromosome (chr) 8. Histopathology with Nissl stains documents substantial abnormalities of upper and lower motor neurons, and there is retinal degeneration beginning in the first month, even without light exposure. Increasing levels of autofluorescent lipopigment are found in both neuronal and non\u2010neuronal tissues as the <jats:italic>mnd<\/jats:italic> mice age. Recently, NCL\u2010like inclusions and accumulating subunit <jats:italic>c<\/jats:italic> have also been described.<\/jats:p><jats:p>When <jats:italic>mnd<\/jats:italic> is outcrossed to the AKR\/J genetic background, ca. 40% of the <jats:italic>mnd<\/jats:italic>\/<jats:italic>mnd<\/jats:italic> F2 progeny show early onset (onset by 4.5\u20105 months and death by 7 months.) This accelerated timing effect seems to be strainspecific, and unlinked to the <jats:italic>mnd<\/jats:italic> gene itself. Our current working hypothesis is that the timing effect is due to 2 or 3 unlinked dominant genes with incomplete penetrance at any single locus. In a combined RFLP\/PCR fragment genetic analysis, the strongest deviation from the expected ratio of AKR vs B6 alleles occurs with markers on proximal half of chr 1. Additional loci on chrs 5 and 10 may also be involved. The mechanism of interaction of these modifying genes with the primary <jats:italic>mnd<\/jats:italic> gene may offer new therapeutic avenues. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.1320570251","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T18:01:48Z","timestamp":1118512908000},"page":"361-364","source":"Crossref","is-referenced-by-count":24,"title":["Genetics of primary and timing effects in the <i>mnd<\/i> mouse"],"prefix":"10.1002","volume":"57","author":[{"given":"A.","family":"Messer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Plummer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. C.","family":"MacMillen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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