Translational Relevance of Animal Models for the Study of Organic Cation Transporter Function



In the mammalian organs, the members of SLC22 family of organic cation transporters (OCTs) mediate distribution, absorption, reabsorption, and secretion of various endogenous and xenobiotic organic cations. OCTs are also responsible for drug–drug interactions and drug-induced organ toxicity. In translational studies, various animal models have been used to study the OCTs-related pathogenesis of human diseases at molecular and cellular level, and to develop new therapeutic drugs and strategies. Particularly useful in this research proved to be mice with the inactivated genes (knockout mice) for specific OCTs. However, some findings in animal models have an uncertain significance for human conditions and diseases, because specific OCTs in their organs exhibit sex differences in protein and/or mRNA expression and species differences in cellular distribution, substrate selectivity and affinity, levels of mRNA and/or protein expression, sensitivity to inhibitors, and regulation. In comparison with animal models, in the human organs some OCTs are absent, others exhibit different localization in the cell membrane domains and different levels of expression, sensitivity to inhibitors, and rates and regulation of the transport of substrates, and none of the thus far tested exhibited the sex-dependent expression. The data from animal models initiated genetic studies in humans, which revealed that several wellknown conditions and diseases are associated with disfunctional OCTs due to gene polymorphism.


Drosophila melanogaster Gene polymorphism Human diseases Humanized mice Knockout mice Organic cation transporters Caenorhabditis elegans Malpighian tubules SLC22 family of transporters Species differences Sex differences Translational research Zebrafish 


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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Molecular Toxicology UnitInstitute for Medical Research and Occupational HealthZagrebCroatia
  2. 2.Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental ResearchRudjer Bošković InstituteZagrebCroatia

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