{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T11:01:58Z","timestamp":1649070118915},"reference-count":0,"publisher":"Hindawi Limited","issue":"2","license":[{"start":{"date-parts":[[1999,10,1]],"date-time":"1999-10-01T00:00:00Z","timestamp":938736000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genet. Res."],"published-print":{"date-parts":[[1999,10]]},"abstract":"<jats:p>The murine <jats:italic>t<\/jats:italic> complex on chromosome 17 contains a number of homozygous lethal and semi-lethal \nmutations that disrupt development of the mouse embryo. We recently characterized an embryonic \nlethality in the rat that results from a germ-line mutation in the tuberous sclerosis 2 (<jats:italic>Tsc-2<\/jats:italic>) \ntumour suppressor gene (the Eker mutation). Remarkably, mouse embryos homozygous for <jats:italic>t<\/jats:italic><jats:sup><jats:italic>w8<\/jats:italic><\/jats:sup> \nmutation display cranial defects reminiscent of those observed in rat embryos homozygous for the \nEker mutation. To determine whether the <jats:italic>Tsc-2<\/jats:italic> gene, which is in the <jats:italic>t<\/jats:italic> \ncomplex, is mutated in <jats:italic>t<\/jats:italic><jats:sup><jats:italic>w8<\/jats:italic><\/jats:sup> \nor other <jats:italic>t<\/jats:italic> haplotypes, we characterized this gene in a series of \n<jats:italic>t<\/jats:italic> haplotype mice. Four <jats:italic>Tsc-2<\/jats:italic> \npolymorphisms were identified: three in the coding region and one intronic that appeared to be \ncommon to all <jats:italic>t<\/jats:italic> haplotypes analysed. No evidence was found to argue that the <jats:italic>Tsc-2<\/jats:italic> gene is \naltered in <jats:italic>t<\/jats:italic><jats:sup><jats:italic>w8<\/jats:italic><\/jats:sup> haplotype mice. However, in the \n<jats:italic>t<\/jats:italic><jats:sup><jats:italic>w5<\/jats:italic><\/jats:sup> haplotype we found a G to T mutation in <jats:italic>Tsc-2<\/jats:italic> \nthat was present only in this <jats:italic>t<\/jats:italic> haplotype. In contrast to other polymorphisms within the <jats:italic>Tsc-2<\/jats:italic> \ncoding region which did not result in amino acid changes in <jats:italic>Tsc-2<\/jats:italic> gene product tuberin, this \nmutation substituted a phenylalanine for a conserved cysteine in <jats:italic>t<\/jats:italic><jats:sup><jats:italic>w5<\/jats:italic><\/jats:sup> \ntuberin. Within the <jats:italic>t<\/jats:italic> complex, the <jats:italic>Tsc-2<\/jats:italic> gene and the putative \n<jats:italic>t<\/jats:italic><jats:sup><jats:italic>w5<\/jats:italic><\/jats:sup> locus appeared to map to different positions, complicating \nidentification of <jats:italic>Tsc-2<\/jats:italic> as a candidate for the <jats:italic>t<\/jats:italic><jats:sup><jats:italic>w5<\/jats:italic><\/jats:sup> \nlocus and suggesting that the G to T mutation in \nthe <jats:italic>Tsc-2<\/jats:italic> gene may have arisen independently of the <jats:italic>t<\/jats:italic><jats:sup><jats:italic>w5<\/jats:italic><\/jats:sup> \nfunctional mutation.<\/jats:p>","DOI":"10.1017\/s0016672399003985","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T13:23:20Z","timestamp":1027776200000},"page":"139-144","source":"Crossref","is-referenced-by-count":1,"title":["Genetic variants of the tuberous sclerosis 2 tumour \nsuppressor gene in mouse <i>t<\/i> haplotypes"],"prefix":"10.1155","volume":"74","author":[{"given":"ELENA V.","family":"KLEYMENOVA","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JEFFREY E.","family":"DECLUE","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"CHERYL L.","family":"WALKER","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"98","published-online":{"date-parts":[[1999,10,1]]},"container-title":["Genetical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0016672399003985","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T22:45:35Z","timestamp":1609454735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0016672399003985\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,10]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1999,10]]}},"alternative-id":["S0016672399003985"],"URL":"https:\/\/doi.org\/10.1017\/s0016672399003985","relation":{},"ISSN":["0016-6723","1469-5073"],"issn-type":[{"value":"0016-6723","type":"print"},{"value":"1469-5073","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,10]]}}}