Funktionsanalyse des Zinktransporters I (ZnT-1) mittels genetischer Deletion

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Zinc is an essential part of proteins estimated to compromise 3 % to 10 % of the human genome. Surprisingly little is known on the regulation of its cytosolic concentrations. Two protein families have been implicated in zinc transport- The ZnT family lowers cytosolic zinc concentrations, whereas the Zip protein family promotes the transport of zinc from the extracellular space or from vesicles to the cytosol. Among the ZnT proteins, ZnT-1 and ZnT-10, that were not studied at all, are the only transporter present at the plasma membrane. ZnT-1 has been envisioned to transport zinc from the cytosol to the extracellular space. However, the evidence for the exchange function are scarce and poor. In addition, neither the counter ion nor the energy source necessary for the transport has been identified. Recent evidence suggests that ZnT-1 is widely expressed in cells that contain the high voltage activated calcium channels. ZnT-1 affects L-type calcium currents in heart, PC12, HEK293, POGRS1 granulosa cells and Xenopus oocytes. The mechanism of interaction is unclear and may depend on an interaction between the Cav β subunit and ZnT-1. Conventional inactivation of the murine ZnT-1 gene Slca1 results in embryonic lethality. We have constructed a conditional Cre-lox based vector that will allow tissue specific deletion of the Slca1 gene to generate mice that lack the ZnT-1 protein either in the heart or the brain.