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Role of ELOVL4 and very long-chain polyunsaturated fatty acids in mouse models of Stargardt type 3 retinal degenerationBarabas, Peter ...Stargardt type 3 (STGD3) disease is a juvenile macular dystrophy caused by mutations in the ELOVL4 (Elongation of very long chain fatty acids 4) gene. Its protein product, ELOVL4, is an elongase ... required for the biosynthesis of very long-chain polyunsaturated fatty acids (VLC-PUFAs). It is unclear whether photoreceptor degeneration in STGD3 is caused by loss of VLC-PUFAs or by mutated ELOVL4 protein trafficking/aggregation. We therefore generated conditional knockout (cKO) mice with Elovl4 ablated in rods or cones and compared their phenotypes to transgenic (TG) animals that express the human STGD3-causing ELOVL4STGD3 allele. Gas chromatographymass spectrometry was used to assess C30C34 VLC-PUFA and N-retinylidene-N-retinylethanolamine content; electroretinography was used to measure phototransduction and outer retinal function; electron microscopy was used for retinal ultrastructure; and the optomotor tracking response was used to test scotopic and photopic visual performance. Elovl4 transcription and biosynthesis of C30C34 VLC-PUFAs in rod cKO and TG retinas were reduced up to 98%, whereas the content of docosahexaenoic acid was diminished in TG, but not rod cKO, retinas. Despite the near-total loss of the retinal VLC-PUFA content, rod and cone cKO animals exhibited no electrophysiological or behavioral deficits, whereas the typical rodcone dystrophic pattern was observed in TG animals. Our data suggest that photoreceptor-specific VLC-PUFA depletion is not sufficient to induce the STGD3 phenotype, because depletion alone had little effect on photoreceptor survival, phototransduction, synaptic transmission, and visual behavior.Vir: Proceedings of the National Academy of Sciences of the United States of America. - ISSN 0027-8424 (Vol. 110, iss. 13, 2013, str. 5181-5186)Vrsta gradiva - članek, sestavni del ; neleposlovje za odrasleLeto - 2013Jezik - angleškiCOBISS.SI-ID - 30522329
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vir: Proceedings of the National Academy of Sciences of the United States of America. - ISSN 0027-8424 (Vol. 110, iss. 13, 2013, str. 5181-5186)
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Ime baze podatkov | Področje | Leto |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Barabas, Peter | ![]() |
Liu, Aihua | ![]() |
Xing, Wei | ![]() |
Križaj, David | 07133 |
Vir: Osebne bibliografije
in: SICRIS
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