@article{LiedtkeHofmannJakobetal.2020,
  author    = {Liedtke, Daniel and Hofmann, Christine and Jakob, Franz and Klopocki, Eva and Graser, Stephanie},
  title     = {Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease},
  series = {Biomolecules},
  volume    = {10},
  journal   = {Biomolecules},
  number    = {12},
  publisher = {MDPI},
  issn      = {2218-273X},
  doi       = {10.3390/biom10121648},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220096},
  year      = {2020},
  abstract  = {Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitously expressed enzyme that is best known for its role during mineralization processes in bones and skeleton. The enzyme metabolizes phosphate compounds like inorganic pyrophosphate and pyridoxal-5′-phosphate to provide, among others, inorganic phosphate for the mineralization and transportable vitamin B6 molecules. Patients with inherited loss of function mutations in the ALPL gene and consequently altered TNAP activity are suffering from the rare metabolic disease hypophosphatasia (HPP). This systemic disease is mainly characterized by impaired bone and dental mineralization but may also be accompanied by neurological symptoms, like anxiety disorders, seizures, and depression. HPP characteristically affects all ages and shows a wide range of clinical symptoms and disease severity, which results in the classification into different clinical subtypes. This review describes the molecular function of TNAP during the mineralization of bones and teeth, further discusses the current knowledge on the enzyme's role in the nervous system and in sensory perception. An additional focus is set on the molecular role of TNAP in health and on functional observations reported in common laboratory vertebrate disease models, like rodents and zebrafish.},
  language  = {en}
}
@article{ZinkSeewaldRohrbachetal.2022,
  author    = {Zink, Miriam and Seewald, Anne and Rohrbach, Mareike and Brodehl, Andreas and Liedtke, Daniel and Williams, Tatjana and Childs, Sarah J. and Gerull, Brenda},
  title     = {Altered expression of TMEM43 causes abnormal cardiac structure and function in zebrafish},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {17},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23179530},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286025},
  year      = {2022},
  abstract  = {Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disease caused by heterozygous missense mutations within the gene encoding for the nuclear envelope protein transmembrane protein 43 (TMEM43). The disease is characterized by myocyte loss and fibro-fatty replacement, leading to life-threatening ventricular arrhythmias and sudden cardiac death. However, the role of TMEM43 in the pathogenesis of ACM remains poorly understood. In this study, we generated cardiomyocyte-restricted transgenic zebrafish lines that overexpress eGFP-linked full-length human wild-type (WT) TMEM43 and two genetic variants (c.1073C>T, p.S358L; c.332C>T, p.P111L) using the Tol2-system. Overexpression of WT and p.P111L-mutant TMEM43 was associated with transcriptional activation of the mTOR pathway and ribosome biogenesis, and resulted in enlarged hearts with cardiomyocyte hypertrophy. Intriguingly, mutant p.S358L TMEM43 was found to be unstable and partially redistributed into the cytoplasm in embryonic and adult hearts. Moreover, both TMEM43 variants displayed cardiac morphological defects at juvenile stages and ultrastructural changes within the myocardium, accompanied by dysregulated gene expression profiles in adulthood. Finally, CRISPR/Cas9 mutants demonstrated an age-dependent cardiac phenotype characterized by heart enlargement in adulthood. In conclusion, our findings suggest ultrastructural remodeling and transcriptomic alterations underlying the development of structural and functional cardiac defects in TMEM43-associated cardiomyopathy.},
  language  = {en}
}