Animals can survive and proliferate under continual environmental temperature changes, by receiving temperature information and processing previous temperature experience. We are studying about molecular physiological mechanism of cold tolerance. Wild-type animals can not survive at 2 degree after cultivation at 25 degree, however, 15 degree-cultivated animals can survive at 2 degree. In order to isolate the molecules involved in cold tolerance, we used DNA microarray analysis. The expression level of
flp-17 gene was significantly changed by temperature stimuli, and then RB2575
flp-17(
ok3587) animals showed defective cold tolerance. However, abnormal cold tolerance of
flp-17(
ok3587) was not restored by the expression of
flp-17 genomic gene. Besides, another null mutant
flp-17(
n4894) showed normal cold tolerance. We therefore hypothesized that background mutation(s) excepting
flp-17(
ok3587) causes defective cold tolerance. We decoded whole genome sequence of RB2575
flp-17(
ok3587) mutant, by using next generation DNA sequencer. Through the SNP analysis, we found that responsible gene of abnormal cold tolerance in RB2575 was F55B11.1 gene. F55B11.1 protein is highly homologues to Xanthine dehydrogenase (XDH) and then we officially named this gene
xdh-1. RB2575 strain has a severe mutation in
xdh-1, and
xdh-1 null mutant showed abnormal cold tolerance. Defective cold tolerance of both RB2575 and
xdh-1 mutants were rescued by genomic
xdh-1 gene. Rescuable genomic
xdh-1::GFP reporter was expressed in some neurons in the head, intestine and excretory cell. To determine the responsible cells and tissues for defective cold tolerance in
xdh-1 mutant, we performed a cell-specific rescue experiment by expressing xdh-1cDNA under driven by specific tissue promoters. We found that abnormal cold tolerance of
xdh-1 mutant was rescued by expressing XDH in neurons but not in excretory cell or intestine. We are trying to identify specific neurons for XDH-dependent cold tolerance. Since xanthine dehydrogenase (XDH) produces uric acid known as an antioxidant causing ROS accumulation, we speculated that ROS accumulation in specific neuron causes abnormal cold tolerance.