Feasibility Analysis of Himalayana Marmot as an Alternative Model of Drug Mitochondrial Toxicity Evaluation

doi:10.3969/j.issn.1674-5817.2012.05.014

Abstract

Abstract: Objective To explore whether Marmots himalayana could replace woodchuck as an alternative model for evaluating the toxicity of nucleotide analogue drugs, the phylogenetic relation of Marmots himalayana with other Marmots were analyzed based on a molecular marker, mitochondrial cytochrome b (Cytb) gene. Methods Cytb genes from Marmots himalayana were sequenced and phylogenetic analysis were performed combined with existing Marmots Cytb gene sequences. Results The Cytb gene of Marmots himalayana was composed of 1140bp nucleotides, in which the average content of A, T, C and G was 33.2%, 25.4%, 28.8%, 12.6% respectively. Significant nucleotides and amino acids bias in Marmots Cytb genes were found: the content of G was significantly lower than that of A, T and C, the usage frequencies of leucine (Leu) and isoleucine (Ile) (11.87% and 15.69% respectively) were significantly higher than that of cysteine (Cys) (1.08%) in all marmots. However, the usage frequencies of isoleucine (Ile, 11.87%) and cysteine (Cys, 1.32%) in Cytb gene of Marmots himalayana from Qinghai-Tibet Plateau were significantly higher than that of other Marmotas. Phylogenetic analysis showed that Chinese M.himalayana, M.sibirica, M.caudata and M.bobak has a close genetic relationship with North America Marmots (Woodchuck), suggesting they were originated from the same species group.Conclusion A close genetic relationship was found between Marmots Himalayana and woodchuck, which provide new evidence for establishing an alternative model for evaluating nucleotide analogue drugs using Marmots Himalayana.

Key words: Marmota Himalayana, Mitochondria, Cytochrome b gene, Phylogeny

CLC Number:

Q959Q95-33

ZHANG Ping-hu, TAO Yuan-qing, JIANG Zhen-zhou, WANG Zhong-dong, FAN Wei, ZHANG Lu-yong. Feasibility Analysis of Himalayana Marmot as an Alternative Model of Drug Mitochondrial Toxicity Evaluation[J]. Laboratory Animal and Comparative Medicine, 2012, 32(5): 436-440.

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