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Taurine deficiency and apoptosis: findings from the taurine transporter knockout mouse
Ulrich Warskulat1, Elena Borsch, Roland Reinehr
1Department of Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University Düsseldorf, Germany. warskulat@med.uni-duesseldorf.de
Abstract:
Apoptosis is characterized by cell shrinkage, nuclear condensation, DNA-fragmentation and apoptotic body formation. Compatible organic osmolytes, e.g. taurine, modulate the cellular response to anisotonicity and may protect from apoptosis. Taurine transporter knockout mice (taut-/- mice) show strongly decreased taurine levels in a variety of tissues. They develop clinically important age-dependent diseases and some of them are characterized by apoptosis. Increased photoreceptor apoptosis leads to blindness of taut-/- mice at an early age. The taurine transporter may not be essential for the differentiation of photoreceptor cells, but many mature cells do not survive without an intact taurine transporter. The olfactory epithelium of taut-/- mice also exhibits structural and functional abnormalities. When compared with wild-types, taut-/- mice have a significantly higher proliferative activity of immature olfactory receptor neurons and an increased number of apoptotic cells. This is accompanied by electrophysiological findings indicating a reduced olfactory sensitivity. Furthermore, taut-/- and taut+/- mice develop moderate unspecific hepatitis and liver fibrosis beyond 1 year of age where hepatocyte apoptosis and activation of the CD95 system are pronounced.
Insights
Taurine transporter knockout mice exhibit increased apoptosis, leading to blindness and olfactory dysfunction. This highlights the critical role of taurine in cellular survival and preventing age-dependent diseases.
Area of Science:
- Cell Biology
- Physiology
- Biochemistry
Background:
- Apoptosis, a programmed cell death, involves characteristic cellular changes.
- Compatible organic osmolytes like taurine can protect cells from apoptosis.
- Taurine transporter knockout (taut-/-) mice have significantly reduced taurine levels.
Purpose of the Study:
- To investigate the role of the taurine transporter in age-dependent diseases characterized by apoptosis in taut-/- mice.
- To examine the impact of taurine deficiency on photoreceptor cells, olfactory epithelium, and liver function.
Main Methods:
- Utilizing taurine transporter knockout (taut-/-) mouse models.
- Observing age-dependent diseases and cellular apoptosis.
- Assessing photoreceptor cell survival, olfactory epithelium structure and function, and liver pathology.
Main Results:
- Taut-/- mice display increased photoreceptor apoptosis, causing early blindness.
- Abnormalities in olfactory epithelium include increased proliferation of immature neurons and heightened apoptosis, leading to reduced olfactory sensitivity.
- Hepatocyte apoptosis and CD95 system activation are pronounced in taut-/- and taut+/- mice, resulting in hepatitis and liver fibrosis.
Conclusions:
- The taurine transporter is crucial for the survival of mature cells, particularly photoreceptors and hepatocytes.
- Taurine deficiency contributes to age-dependent diseases, including blindness, olfactory dysfunction, and liver pathology.
- The CD95 system plays a role in the pronounced hepatocyte apoptosis observed in taurine-deficient mice.
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