24.09.19 12:48

Two publications on deficiency of the taurine transporter molecule lead to unexpected results

Taurine transporters in mice and humans

By: Editorial staff

The amino acid taurine is found in large quantities in the cells of the brain, liver and other organs. It serves to regulate cell volume, has antioxidative properties and stablises proteins in those organs. Other functions for the organism have not yet been conclusively determined.

Düsseldorf-based scientists working under renowned hepatologist Prof. Dr. Dieter Häussinger have now presented a further publication on this topic. In the current edition of the journal PNAS (Proceedings of the National Academy of Sciences of the United States of America), they describe together with senior author Prof. Dr. Dieter Häussinger and first author Dr. Natalia Qvartskhava the consequences of extremely low concentrations of the amino acid taurine as serious abnormalities. They based their research on what are referred to as ‘knock-out mice’ (KO mice), which have been subjected to targeted genetic modifications and have a pronounced deficiency of the taurine transporter molecule TauT due to a mutation of their genes. This transporter normally ensures that high intracellular taurine concentrations are maintained.

As shown by Prof. Häussinger and his group already years ago, the KO mice develop early-onset and progressive retinal degeneration leading to blindness as well as other sensory, heart and muscle problems. Their oxidative stress is enhanced. These clinical abnormalities increase as the animals get older. The most important finding from the recently published work is that all of the animals also suffer from hyperammonemia, i.e. excessive concentrations of ammonium, as liver detoxification performance is significantly impaired as a result of the taurine deficiency.

By sheer coincidence, the researchers are now also able to report on consequences of taurine deficiency in humans at almost the same time and have thus provided the first description of this previously unknown disease. In another contribution (The FASEB Journal), produced together with collaborating institutes, they have published an article about two boys, brothers from a family with consanguineous parents, who at the ages of eleven and four already suffer from retinal degeneration on account of a mutation of the SLC6A6 gene as in the KO mouse model. The mutation was inherited from both parents. Like in the animal model, this genetic defect has caused damage to the brothers’ retina with significant impairment of their vision. The reason for this is low taurine levels.

Generally taurine is an amino acid found in cells and in the blood. It stabilises proteins in the body’s cells. If the organism fails to produce enough of the taurine transporter molecule TauT, which ensures transport of the amino acid through the cell membrane, this leads to low taurine levels in the tissue. In KO mice this severely impaired vision, hearing and sense of smell as well as brain, heart and muscle function, and leads to hyperammonemia. These symptoms increased as the mice got older, ultimately potentially manifesting as liver fibrosis or even liver cancer.

There are obviously parallels in the effects of taurine deficiency on the human organism. The two brothers came to the attention of staff at University Hospital Gießen when they presented for eye examinations there. They were also examined by medical geneticist Hanno J. Bolz, Senckenberg Centre for Human Genetics, Frankfurt a. M., who contacted the hepatologists in Düsseldorf. The children were subsequently examined in Düsseldorf by six institutions involved in the collaborative research center CRC 974 “Communication and System Relevance in Liver Injury and Regeneration” at HHU Düsseldorf. The spokesperson for the CRC 974 is Prof. Dr. Dieter Häussinger, Director of the Department of Gastroenterology, Hepatology and Infectiology, University Hospital Düsseldorf: “We were able to examine the children in just one day at the University Hospital. That was only possible thanks to the collaboration in our CRC 974. But the children were great, too. They were very cooperative in completing the programme. For them, the findings mean that we have a good idea of what we need to watch out for in the future,” says Häussinger, “the long-term impact of taurine deficiency on the human organism remains to be seen.” The collaboration also included the Department of Ophthalmology at Justus Liebig University Gießen, specialised institutes at the University of Cologne, institutes at Mainz University and the John von Neumann Institute at Forschungszentrum Jülich.

“The direct comparison between the basic research hepatological findings and the clinical manifestation of the same mutation in humans can and will provide insights that we did not expect to have so soon,” says Prof. Häussinger.

 

 Original publications:

·         Taurine transporter (TauT) deficiency impairs ammonia detoxification in mouse liver. Qvartskhava N, Jin CJ, Buschmann T, Albrecht U, Bode JG, Monhasery N, Oenarto J, Bidmon HJ, Görg B, Häussinger D. Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6313-6318. doi: 10.1073/pnas.1813100116. Epub 2019 Mar 12. PMID: 30862735

·         Preising MN, Görg B, Friedburg C, Qvartskhava N, Budde BS, Bonus M, Toliat MR, Pfleger C, Altmüller J, Herebian D, Beyer M, Zöllner HJ, Wittsack HJ, Schaper J, Klee D, Zechner U, Nürnberg P, Schipper J, Schnitzler A, Gohlke H, Lorenz B, Häussinger D, Bolz HJ. FASEB J. 2019; doi: 10.1096/fj.201900914RR.

 

Contact: Prof. Dr. Dieter Häussinger, Director of the Department of Gastroenterology, Hepatology and Infectiology, University Hospital Düsseldorf, Tel.: 0211 / 81-16330, e-mail: haeussin@uni-duesseldorf.de

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