ArticleProceedings of the National Academy of Sciences of the United States of America2005
Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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Who cites it
116 citing papers in PubMed, 306 citations in OpenAlex.
- Functional screening of ZIP8 naturally occurring variants identifies pathogenic mutations and trafficking defects.The Journal of biological chemistry · 2026Article
- Study on the Accumulation, Excretion, and Distribution of Cadmium in Mice After Dietary Exposure to Cadmium-Rich Swimming CrabFoods (Basel, Switzerland) · 2026Article
- Semen Quality in a Large Cohort of Males Living in Highly Polluted Areas of Campania Region in Southern Italy with a Focus on the Role of Cadmium Exposure.Journal of clinical medicine · 2026Article
- Manganese: biology, physiology and role in disease.Cell discovery · 2026Review
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- Functional screening of ZIP8 naturally occurring variants identifies pathogenic mutations and trafficking defects.bioRxiv : the preprint server for biology · 2026Article
- Combatting Cadmium Toxicity in Animals with Nature-Derived Remedies: Mechanisms and Mitigation.Biological trace element research · 2026Review
- Review
- Cadmium Uptake into Rat Osteoblast UMR-106 Cells is Mediated via Multiple Pathways.Biological trace element research · 2026Article
- Junctions, Transporters, and Interactions of Endothelial Cells: Regulation by Ethanol.International journal of molecular sciences · 2026Review
- Bitter Taste Receptors TAS2R8 and TAS2R10 Reduce Proton Secretion and Differentially Modulate Cadmium Uptake in Immortalized Human Gastric Cells.International journal of molecular sciences · 2025Article
- Ion-Induced Dipole Interactions Matter in Metadynamics Simulation of Transition Metal Ion Transporters.Journal of chemical theory and computation · 2025Article
- Neuronal SLC39A8 deficiency impairs cerebellar development by altering manganese homeostasis.JCI insight · 2024Article
- Evolution, classification, and mechanisms of transport, activity regulation, and substrate specificity of ZIP metal transporters.Critical reviews in biochemistry and molecular biology · 2024Review
- Integrating Transcriptomics and Proteomics to Characterize the Intestinal Responses to Cadmium Exposure Using a Piglet Model.International journal of molecular sciences · 2024Article
- The manganese transporter SLC39A8 links alkaline ceramidase 1 to inflammatory bowel disease.Nature communications · 2024Article
- Research progress on the molecular structure, function, and application in tumor therapy of zinc transporter ZIP4.International journal of biological sciences · 2024Review
- Rational engineering of an elevator-type metal transporter ZIP8 reveals a conditional selectivity filter critically involved in determining substrate specificity.Communications biology · 2023Article
- The role of Zn2+ in shaping intracellular Ca2+ dynamics in the heart.The Journal of general physiology · 2023Review
- Zinc and selenium attenuate quaternary heavy metal mixture-induced testicular damage via amplification of the antioxidant system, reduction in metal accumulation, inflammatory and apoptotic biomarkers.Toxicological research · 2023Article
56 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Testicular necrosis is a sensitive endpoint for cadmium (Cd(2+), Cd) toxicity across all species tested. Resistance to Cd-induced testicular damage is a recessive trait assigned to the Cdm locus on mouse chromosome 3. We first narrowed the Cdm-gene-containing region to 880 kb. SNP analysis of this region from two sensitive and two resistant inbred strains demonstrated a 400-kb haplotype block consistent with the Cd-induced toxicity phenotype; in this region is the Slc39a8 gene encoding a member of the solute-carrier superfamily. Slc39a8 encodes SLC39A8 (ZIP8), whose homologs in plant and yeast are putative zinc transporters. We show here that ZRT-, IRT-like protein (ZIP)8 expression in cultured mouse fetal fibroblasts leads to a >10-fold increase in the rate of intracellular Cd influx and accumulation and 30-fold increase in sensitivity to Cd-induced cell death. The complete ZIP8 mRNA and intron-exon splice junctions have no nucleotide differences between two sensitive and two resistant strains of mice; by using situ hybridization, we found that ZIP8 mRNA is prominent in the vascular endothelial cells of the testis of the sensitive strains of mice but absent in these cells of resistant strains. Slc39a8 is therefore the Cdm gene, defining sensitivity to Cd toxicity specifically in vascular endothelial cells of the testis.
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