Slc30a10-KO Mouse

Slc30a10, a manganese (Mn) efflux transporter, is crucial for maintaining Mn homeostasis. It is involved in excreting Mn from hepatocytes into bile and from enterocytes into the gastrointestinal tract lumen, thus preventing Mn toxicity [3,5,7]. Mutations in this gene can lead to familial parkinsonism associated with Mn retention and other severe symptoms, highlighting its significance in preventing Mn-induced neurotoxicity and related disorders [3,4,6]. Genetic models, such as knockout (KO) mice, have been instrumental in studying its function [1,2,5].

In pan-neuronal/glial Slc30a10 knockout mice, Mn levels were elevated in specific brain regions during early postnatal development, and adolescent or adult knockouts exhibited neuromotor deficits and reduced striatal dopamine release without neurodegeneration or changes in striatal dopamine levels. This indicates that brain Slc30a10 regulates Mn levels in early postnatal life, protecting against deficits in neuromotor function and dopaminergic neurotransmission [1]. Whole-body Slc30a10-deficient mice developed severe Mn excess and impaired systemic and biliary Mn excretion, while liver-or small intestine-specific knockouts had less severe Mn excess, suggesting that Slc30a10 in these tissues is essential for Mn excretion [5].

In conclusion, Slc30a10 is essential for Mn excretion and maintaining Mn homeostasis, protecting against Mn-induced toxicity. Studies using KO mouse models have revealed its role in preventing deficits in neuromotor function, dopaminergic neurotransmission, and in physiological Mn excretion. Understanding Slc30a10 function is crucial for treating Mn-related diseases, such as familial parkinsonism and Mn-induced neurotoxicity.

References:

1. Taylor, Cherish A, Grant, Stephanie M, Jursa, Thomas, Gonzales, Rueben A, Mukhopadhyay, Somshuvra. . SLC30A10 manganese transporter in the brain protects against deficits in motor function and dopaminergic neurotransmission under physiological conditions. In Metallomics : integrated biometal science, 15, . doi:10.1093/mtomcs/mfad021. https://pubmed.ncbi.nlm.nih.gov/36990693/

2. Prajapati, Milankumar, Pettiglio, Michael A, Conboy, Heather L, Fukada, Toshiyuki, Bartnikas, Thomas B. 2021. Characterization of in vitro models of SLC30A10 deficiency. In Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 34, 573-588. doi:10.1007/s10534-021-00296-y. https://pubmed.ncbi.nlm.nih.gov/33713241/

3. Mukhopadhyay, Somshuvra. 2017. Familial manganese-induced neurotoxicity due to mutations in SLC30A10 or SLC39A14. In Neurotoxicology, 64, 278-283. doi:10.1016/j.neuro.2017.07.030. https://pubmed.ncbi.nlm.nih.gov/28789954/

4. Chen, Pan, Bowman, Aaron B, Mukhopadhyay, Somshuvra, Aschner, Michael. 2015. SLC30A10: A novel manganese transporter. In Worm, 4, e1042648. doi:10.1080/21624054.2015.1042648. https://pubmed.ncbi.nlm.nih.gov/26430566/

5. Mercadante, Courtney J, Prajapati, Milankumar, Conboy, Heather L, Rao, Deepa B, Bartnikas, Thomas B. . Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity. In The Journal of clinical investigation, 129, 5442-5461. doi:10.1172/JCI129710. https://pubmed.ncbi.nlm.nih.gov/31527311/

6. Carmona, Asuncion, Zogzas, Charles E, Roudeau, Stéphane, Mukhopadhyay, Somshuvra, Ortega, Richard. 2018. SLC30A10 Mutation Involved in Parkinsonism Results in Manganese Accumulation within Nanovesicles of the Golgi Apparatus. In ACS chemical neuroscience, 10, 599-609. doi:10.1021/acschemneuro.8b00451. https://pubmed.ncbi.nlm.nih.gov/30272946/

7. Prajapati, Milankumar, Zhang, Jared Z, Chiu, Lauren, Aghajan, Mariam, Bartnikas, Thomas B. 2024. Hepatic HIF2 is a key determinant of manganese excess and polycythemia in SLC30A10 deficiency. In JCI insight, 9, . doi:10.1172/jci.insight.169738. https://pubmed.ncbi.nlm.nih.gov/38652538/