{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T06:45:56Z","timestamp":1778136356914,"version":"3.51.4"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,12]],"date-time":"2006-01-12T00:00:00Z","timestamp":1137024000000},"content-version":"vor","delay-in-days":407,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>: <\/jats:bold> Functions of \u03b1\u2010tocopherol (\u03b1\u2010T) <jats:italic>in vivo<\/jats:italic>, other than those for fertility in females, are intensely debated. The discovery of \u03b1\u2010T deficiency in patients with ataxia (AVED) followed by the identification of mutations in the gene encoding \u03b1\u2010tocopherol transfer protein (TTP) in AVED patients demonstrates an essential role of \u03b1\u2010T and TTP for normal neurological function. \u03b1\u2010T molecular targets that account for \u03b1\u2010T\u2010sensitive neurological dysfunction remain to be discovered. We have used high\u2010density oligonucleotide arrays to search for putative \u03b1\u2010T\u2010sensitive genes in the CNS and other tissues in an <jats:italic>in vivo<\/jats:italic> model of \u03b1\u2010T deficiency imposed at birth by the deletion of the TTP gene in mice. Repression of genes affecting synaptic function and myelination and induction of genes for neurodegeneration in the motor cortex of \u03b1\u2010T\u2010deficient mice were identified. The expression of retinoic acid\u2010related orphan receptor alpha (ROR\u2010\u03b1) was repressed in the cortex and adrenal glands of TTP\u2010deficient mice. Deficiency of ROR\u2010\u03b1 causes ataxia in mice and may account for ataxia in AVED patients. These observations suggest that some of the actions of \u03b1\u2010T are mediated by the transcription factor ROR\u2010\u03b1. The behavior of young TTP\u2010null mice was essentially normal, but older mice showed inactivity, ataxia, and memory dysfunction. mRNA profiles of old \u03b1\u2010T\u2010deficient cerebral cortices are compatible with repressed activity of oligodendrocytes and astrocytes. In conclusion, gene\u2010expression profiling studies have identified novel \u03b1\u2010T\u2010modulated genes and cells in the CNS that may be causatively linked with delayed neurodegeneration and age\u2010related decline in behavioral repertoires.<\/jats:p>","DOI":"10.1196\/annals.1331.012","type":"journal-article","created":{"date-parts":[[2005,3,7]],"date-time":"2005-03-07T19:07:39Z","timestamp":1110222459000},"page":"109-126","source":"Crossref","is-referenced-by-count":53,"title":["\u03b1\u2010Tocopherol Transfer Protein Deficiency in Mice Causes Multi\u2010Organ Deregulation of Gene Networks and Behavioral Deficits with Age"],"prefix":"10.1111","volume":"1031","author":[{"given":"KISHORCHANDRA","family":"GOHIL","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ROY","family":"GODZDANKER","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ERIN","family":"O'ROARK","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"BETTINA C.","family":"SCHOCK","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"RAMESH R.","family":"KAINI","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LESTER","family":"PACKER","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"CARROLL E.","family":"CROSS","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MARET G.","family":"TRABER","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,1,12]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.56.1458.650"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0899-9007(01)00637-2"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.10.1145"},{"key":"e_1_2_6_5_2","doi-asserted-by":"crossref","first-page":"17705","DOI":"10.1016\/S0021-9258(17)46761-5","article-title":"Primary structure of alpha\u2010tocopherol transfer protein from rat liver: homology with cellular retinaldehyde\u2010binding protein","volume":"268","author":"Sato Y.","year":"1993","journal-title":"J. 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