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Gene Review:

MGMT - O-6-methylguanine-DNA methyltransferase

Canis lupus familiaris

Zaboikin, M. et al., Trobridge, G. et al.

Zaboikin, Srinivasakumar, Zaboikina, Schuening,

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Disease relevance of MGMT

Using MGMT selection, long-term marking levels exceeding 50% can now be routinely attained with minimal toxicity [1].

High impact information on MGMT

Proline at position 140 and the surrounding amino acids of the human MGMT are highly conserved in the canine sequence [2].
The human O(6)-methylguanine-DNA methyltransferase (MGMT) gene and its mutants have been used for in vivo selection of transduced hematopoietic stem cells with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) alone or in combination with O(6)-benzylguanine (BG) [2].
Drug resistance assays using BCNU alone or BCNU with BG demonstrated that the wild-type and mutant canine MGMTs provided resistance to the selection agents that was comparable to the human MGMT counterparts [2].

Chemical compound and disease context of MGMT

To date, the best results have been observed with O(6)-methylguanine-DNA methyltransferase (MGMT) selection, with which increases in gene-marked repopulating cells have been maintained long-term, likely because of the toxicity of 1,3-bis-(2-chloroethyl)-1-nitrosourea and temozolomide to quiescent HSCs [1].

References

Hematopoietic stem cell transduction and amplification in large animal models. Trobridge, G., Beard, B.C., Kiem, H.P. Hum. Gene Ther. (2005) [Pubmed]
Cloning and expression of canine O6-methylguanine-DNA methyltransferase in target cells, using gammaretroviral and lentiviral vectors. Zaboikin, M., Srinivasakumar, N., Zaboikina, T., Schuening, F. Hum. Gene Ther. (2004) [Pubmed]

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