Preising, Markus N., Goerg, Boris, Friedburg, Christoph, Qvartskhava, Natalia, Budde, Birgit S., Bonus, Michele, Toliat, Mohammad R., Pfleger, Christopher, Altmueller, Janine, Herebian, Diran ORCID: 0000-0002-8528-0122, Beyer, Mila, Zoellner, Helge J., Wittsack, Hans-Joerg, Schaper, Joerg, Klee, Dirk, Zechner, Ulrich, Nuernberg, Peter, Schipper, Joerg, Schnitzler, Alfons, Gohlke, Holger, Lorenz, Birgit ORCID: 0000-0002-9737-8127, Haeussinger, Dieter and Bolz, Hanno J. (2019). Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration. Faseb J., 33 (10). S. 11507 - 11528. BETHESDA: FEDERATION AMER SOC EXP BIOL. ISSN 1530-6860

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Abstract

We previously reported that inactivation of the transmembrane taurine transporter (TauT or solute carrier 6a6) causes early retinal degeneration in mice. Compatible with taurine's indispensability for cell volume homeostasis, protein stabilization, cytoprotection, antioxidation, and immuno- and neuromodulation, mice develop multisystemic dysfunctions (hearing loss; liver fibrosis; and behavioral, heart, and skeletal muscle abnormalities) later on. Here, by genetic, cell biologic, in vivo H-1-magnetic resonance spectroscopy and molecular dynamics simulation studies, we conducted in-depth characterization of a novel disorder: human TAUT deficiency. Loss of TAUT function due to a homozygous missense mutation caused panretinal degeneration in 2 brothers. TAUT(p.A78E) still localized in the plasma membrane but is predicted to impact structural stabilization. H-3-taurine uptake by peripheral blood mononuclear cells was reduced by 95%, and taurine levels were severely reduced in plasma, skeletal muscle, and brain. Extraocular dysfunctions were not yet detected, but significantly increased urinary excretion of 8-oxo-7,8-dihydroguanosine indicated generally enhanced (yet clinically unapparent) oxidative stress and RNA oxidation, warranting continuous broad surveillance.-Preising, M. N., Gorg, B., Friedburg, C., Qvartskhava, N., Budde, B. S., Bonus, M., Toliat, M. R., Pfleger, C., Altmuller, J., Herebian, D., Beyer, M., Zollner, H. J., Wittsack, H.-J., Schaper, J., Klee, D., Zechner, U., Nurnberg, P., Schipper, J., Schnitzler, A., Gohlke, H., Lorenz, B., Haussinger, D., Bolz, H. J. Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Preising, Markus N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goerg, BorisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedburg, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Qvartskhava, NataliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Budde, Birgit S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bonus, MicheleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toliat, Mohammad R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfleger, ChristopherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herebian, DiranUNSPECIFIEDorcid.org/0000-0002-8528-0122UNSPECIFIED
Beyer, MilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zoellner, Helge J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wittsack, Hans-JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaper, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klee, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zechner, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schipper, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schnitzler, AlfonsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gohlke, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lorenz, BirgitUNSPECIFIEDorcid.org/0000-0002-9737-8127UNSPECIFIED
Haeussinger, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolz, Hanno J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-132718
DOI: 10.1096/fj.201900914RR
Journal or Publication Title: Faseb J.
Volume: 33
Number: 10
Page Range: S. 11507 - 11528
Date: 2019
Publisher: FEDERATION AMER SOC EXP BIOL
Place of Publication: BETHESDA
ISSN: 1530-6860
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MOLECULAR-DYNAMICS SIMULATIONS; RIGIDITY THEORY; ISCEV STANDARD; SOFTWARE; KNOCKOUT; MOUSE; ACCURACY; SODIUM; MODEL; FLEXIBILITYMultiple languages
Biochemistry & Molecular Biology; Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13271

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