Dalton T P, Miller M L, Wu X, Menon A, Cianciolo E, McKinnon R A, Smith P W, Robinson L J, Nebert D W
Department of Environmental Health, University of Cincinnati Medical Center, Ohio 45267-0056, USA.
Pharmacogenetics. 2000 Mar;10(2):141-51. doi: 10.1097/00008571-200003000-00006.
Cadmium (Cd++) is a widespread environmental pollutant and classifed as an IARC 'Category I' human carcinogen. Cd++ can also cause severe renal toxicity and may be involved clinically in cardiovascular disease and osteoporosis. Genetic differences in sensitivity to cadmium toxicity have been noted in humans, whereas, among inbred mouse strains, unequivocal genetic data exist. Resistance to cadmium-induced testicular damage was reported in 1973 to be associated with a single major recessive gene, named Cdm, which has now been localized to mouse chromosome (Chr) 3. Using polymorphic microsatellite markers and semiquantitative histological parameters, we have corroborated the original 1973 data concerning mendelian inheritance and have further refined the region containing the Cdm gene from more than 24 cM to 0.64 cM (estimated 40-80 genes). We phenotyped 26 recombinant inbred lines generated from C57BL/6J (B6, resistant) and DBA/2J (D2, sensitive) inbred mice, and determined that the Cdm gene maps between microsatellite markers D3Mit110 and D3Mit255. Although toxicity to numerous heavy metals is well known, virtually no molecular mechanisms have yet been uncovered either in humans or laboratory animals. Identification and characterization of the mouse Cdm gene should enhance our understanding of heavy metal toxicity by identifying and characterizing, for the first time, a major mammalian gene responsible for susceptibility to diseases caused by heavy metal toxicity.
镉（Cd++）是一种广泛存在的环境污染物，被国际癌症研究机构（IARC）列为“1类”人类致癌物。Cd++还可导致严重的肾毒性，临床上可能与心血管疾病和骨质疏松症有关。人类对镉毒性的敏感性存在遗传差异，而在近交系小鼠品系中，存在明确的遗传数据。1973年报道，对镉诱导的睾丸损伤的抗性与一个单一的主要隐性基因有关，该基因名为Cdm，现已定位到小鼠染色体（Chr）3上。利用多态性微卫星标记和半定量组织学参数，我们证实了1973年关于孟德尔遗传的原始数据，并将包含Cdm基因的区域从超过24厘摩进一步缩小到0.64厘摩（估计有40 - 80个基因）。我们对由C57BL/6J（B6，抗性）和DBA/2J（D2，敏感）近交小鼠产生的26个重组近交系进行了表型分析，并确定Cdm基因位于微卫星标记D3Mit110和D3Mit255之间。尽管对多种重金属的毒性已为人所知，但在人类或实验动物中几乎尚未发现任何分子机制。对小鼠Cdm基因的鉴定和表征应能通过首次鉴定和表征一个负责重金属毒性所致疾病易感性的主要哺乳动物基因，增强我们对重金属毒性的理解。
