Changes in patterns of gene expression in the testis in response to cadmium, a known male reproductive toxicant are being used to: 1) identify primary and secondary gene responses to the toxicant, 2) to identify the initial target cell of the toxicant in the testis, and 3) to use the temporal pattern of changes in gene expression to define the mechanisms of toxicity. ? ? A mouse testis microarray has been developed and is being used in the cadmium studies. It also will be useful for studies of effects of gene knockouts, endocrine manipulations, and other treatments. Eight cDNA libraries constructed with mRNA from mouse testis and germ cells isolated at different stages of development were subjected to single-pass sequencing from the 5' end to identify clones to be used for this purpose. Over 28,000 clones were sequenced and over 22,000 ESTs were deposited in public databases. A mouse testis 22K microarray has been constructed using this sequence information and other information public databases. A comparison of the information gained from using the testis microarray and a whole mouse genome microarray has determined that a substantially larger number of genes on the testis microarray are seen to undergo changes in expression following cadmium treatment than are seen on the whole mouse genome microarray.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES071009-07
Application #
7593960
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2007
Total Cost
$226,379
Indirect Cost
City
State
Country
United States
Zip Code
Zhou, Tong; Jia, Xiaodong; Chapin, Robert E et al. (2004) Cadmium at a non-toxic dose alters gene expression in mouse testes. Toxicol Lett 154:191-200
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Bennett, L M; McAllister, K A; Blackshear, P E et al. (2000) BRCA2-null embryonic survival is prolonged on the BALB/c genetic background. Mol Carcinog 28:174-83