Journal Article

FZJ-2019-04062

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration

Preising, M. N. ; Görg, B. ; Friedburg, C. ; Qvartskhava, N. ; Budde, B. S. ; Bonus, M. ; Toliat, M. R. ; Pfleger, C. ; Altmüller, J. ; Herebian, D. ; Beyer, M. ; Zöllner, H. J. ; Wittsack, H.-J. ; Schaper, J. ; Klee, D. ; Zechner, U. ; Nürnberg, P. ; Schipper, J. ; Schnitzler, A. ; Gohlke, H.FZJ* ; Lorenz, B. ; Häussinger, D. (Corresponding author) ; Bolz, H. J. (Corresponding author)

2019
FASEB Bethesda, Md.

This record in other databases:      

Please use a persistent id in citations: doi:10.1096/fj.201900914RR

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 vivo1H–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. TAUTp.A78E still localized in the plasma membrane but is predicted to impact structural stabilization. 3H-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., Görg, B., Friedburg, C., Qvartskhava, N., Budde, B. S., Bonus, M., Toliat, M. R., Pfleger, C., Altmüller, J., Herebian, D., Beyer, M., Zöllner, H. J., Wittsack, H.-J., Schaper, J., Klee, D., Zechner, U., Nürnberg, P., Schipper, J., Schnitzler, A., Gohlke, H., Lorenz, B., Häussinger, D., Bolz, H. J. Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration.

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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)
2. Jülich Supercomputing Center (JSC)
3. John von Neumann - Institut für Computing (NIC)

Research Program(s):

1. 511 - Computational Science and Mathematical Methods (POF3-511) (POF3-511)
2. Forschergruppe Gohlke (hkf7_20170501) (hkf7_20170501)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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