Deletion of the mouse Fmo1 gene results in enhanced pharmacological behavioural responses to imipramine

Pharmacogenetics and Genomics

Volumn 19, Issue 4, 2009, Pages 289-299

  Hernandez, Diana ^a,b,c   Janmohamed, Azara ^a   Chandan, Pritpal ^a   Omar, Bilal A ^c   Phillips, Ian R ^b,c   Shephard, Elizabeth A ^a,b  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Behavioural response; Chromosomal engineering; Drug metabolism; Flavin containing monooxygenase; Imipramine; Knockout mice; Pharmacogenetics

Indexed keywords

CYTOCHROME P450; DESIPRAMINE; DIMETHYLANILINE MONOOXYGENASE; DRUG METABOLITE; IMIPRAMINE; IMIPRAMINOXIDE;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BEHAVIOR; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG EFFECT; DRUG METABOLISM; DRUG OXIDATION; DRUG RESPONSE; EMBRYO; ENZYME ACTIVITY; FEMALE; FMO1 GENE; GENE; GENE DELETION; KNOCKOUT MOUSE; MALE; MOUSE; MUSCLE SPASM; NONHUMAN; PHARMACOGENETICS; PRIORITY JOURNAL; SINGLE DRUG DOSE; TREMOR;

ANIMALS; ANTIDEPRESSIVE AGENTS, TRICYCLIC; BEHAVIOR, ANIMAL; CELLS, CULTURED; CHROMOSOMES; EMBRYONIC STEM CELLS; FEMALE; GENE DELETION; HETEROZYGOTE; HOMOZYGOTE; IMIPRAMINE; INTEGRASES; MALE; MICE; OXYGENASES; SPASM; TRANSFECTION; TREMOR;

MUS;

EID: 63849173815     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0b013e328328d507     Document Type: Article

References (53)

1. Krueger SK, Williams DE. Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism. Pharmacol Ther 2005; 106:357-387.
2. Cashman JR, Zhang J. Human flavin-containing monooxygenases. Annu Rev Pharmacol Toxicol 2006; 46:65-100.
3. Phillips IR, Francois AA, Shephard EA. The flavin-containing monooxygenases (FMOs): genetic variation and its consequences for the metabolism of therapeutic drugs. Curr Pharmacogenomics 2007; 5:292-313.
4. Phillips IR, Shephard EA. Flavin-containing monooxygenases: mutations, disease and drug response. Trends Pharmacol Sci 2008; 29:294-301.
5. Lemoine A, Gautier JC, Azoulay D, Kiffel L, Belloc C, Guengerich FP, et al. Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver. Mol Pharmacol 1993; 43:827-832.
6. Brosen K, Zeugin T, Meyer UA. Role of P450IID6, the target of the sparteine-debrisoquine oxidation polymorphism, in the metabolism of imipramine. Clin Pharmacol Ther 1991; 49:609-617.
7. Rouer E, Lemoine T, Cresteil P, Rouet P, Leroux JP. Effects of genetic or chemically induced diabetes on imipramine metabolism: respective involvement of flavin monooxygenase and cytochrome P-450-dependent monooxygenases. Drug Metab Dispos 1987; 15:524-528.
8. Kim YM, Ziegler DM. Size limits of thiocarbamides accepted as substrates by human flavin-containing monooxygenase 1. Drug Metab Dispos 2000; 28:1003-1006.
9. Falls JG, Cherrington NJ, Clements KM, Philpot RM, Levi PE, Rose RL, Hodgson E. Molecular cloning, sequencing, and expression in Escherichia coli of mouse flavin-containing monooxygenase 3 (FMO3): comparison with the human isoform. Arch Biochem Biophys 1997; 347:9-18.
10. Cherrington NJ, Cao Y, Cherrington JW, Rose RL, Hodgson E. Physiological factors affecting protein expression of flavin-containing monooxygenases 1, 3 and 5. Xenobiotica 1998; 28:673-682.
11. Devane CL, Wolin RE, Rovere RA, Panahon NC, Sutfin TA, Jusko WJ. Excessive plasma concentration of tricyclic antidepressants resulting from usual doses: a report of six cases. J Clin Psychiatry 1981: 42:143-147.
12. Garvey MJ, Tuason VB, Johnson RA, Valentine RH, Cooper TB. Elevated plasma tricyclic levels with therapeutic doses of imipramine. Am J Psychiatry 1984; 141:853-856.
13. Furnes B, Feng J, Sommer SS, Schlenk D. Identification of novel variants of the flavin-containing monooxygenase gene family in African Americans. Drug Metab Dispos 2003; 31:187-193.
14. Furnes B, Schlenk D. Evaluation of xenobiotic N- and S-oxidation by variant flavin-containing monooxygenase 1 (FMO1) enzymes. Toxicol Sci 2004; 78:196-203.
15. Krause RJ, Lash LH, Elfarra AA. Human kidney flavin-containing monooxygenases and their potential roles in cysteine S-conjugate metabolism and nephrotoxicity. J Pharmacol Exp Ther 2003; 304:185-191.
16. Koukouritaki SB, Hines RN. Flavin-containing monooxygenase genetic polymorphism: impact on chemical metabolism and drug development. Pharmacogenomics 2005; 6:807-822.
17. Hines RN, Luo Z, Hopp KA, Cabacungan ET, Koukouritaki SB, McCarver DG. Genetic variability at the human FMO1 locus: significance of a basal promoter yin yang 1 element polymorphism (FMO1 *6). J Pharmacol Exp Ther 2003; 306:1210-1218.
18. Hernandez D, Janmohamed A, Chandan P, Phillips IR, Shephard EA. Organization and evolution of the flavin-containing monooxygenase genes of human and mouse: identification of novel gene and pseudogene clusters. Pharmacogenetics 2004; 14:117-130.
19. Shephard EA, Chandan P, Stevanovic-Walker M, Edwards M, Phillips IR. Alternative promoters and repetitive DNA elements define the speciesdependent tissue-specific expression of the FMO1 genes of human and mouse. Biochem J 2007; 406:491-499.
20. Beckett AH, Triggs EJ. Buccal absorption of basic drugs and its application as an in vivo model of passive drug transfer through lipid membranes. J Pharm Pharmacol 1967; 19 (Suppl):31S-41S.
21. Midha KK, Jaworski TJ, Hawes EM, McKay G, Hubbard JW, Aravagiri M, Marder SR. Radioimmunoassay and other methods for trace analysis of N-oxide compounds. In: Hlavica P, Damani LA, editors. N-oxidation of drugs biochemistry, pharmacology, toxicology. London: Chapman & Hall; 1991. pp. 37-58.
22. Ziegler DM. Functional groups activated via flavin-containing monooxygenases. ln: Miners JO, Birkett DJ, Drew R, May BK, McManus ME, editors. Microsomes and drug oxidations. London: Taylor and Francis; 1988. pp. 297-304.
23. Hernandez D, Chandan P, Janmohamed A, Phillips IR, Shephard EA. Deletion of genes from the mouse genome using Cre/loxP technology. In: Phillips IR, Shephard EA, editors. Cytochrome P4S0 protocols. 2nd ed. Totowa, New Jersey: Humana Press; 2006. pp. 307-319.
24. O'Gorman S, Dagenais NA, Qian M, Marchuk Y. Protamine-Cre recombinase transgenes efficiently recombine target sequences in the male germ line of mice, but not in embryonic stem cells. Proc Natl Acad Sci USA 1997; 94:14602-14607.
25. Hernandez D, Phillips IR, Shephard EA. Characterization of targeted mouse embryonic stem cell chromosomes: karyotyping and fluorescence in situ hybridization of metaphase spreads. In: Phillips IR, Shephard EA, editors. Cytochrome P450 protocols. 2nd ed. Totowa, New Jersey: Humana Press; 2006. pp. 321-327.
26. Hernandez D, Melidoni AN, Phillips IR, Shephard EA. Microinjection of targeted embryonic stem cells and establishment of knockout mouse lines for Fmo genes. In: Phillips IR, Shephard EA, editors. Cytochrome P450 protocols. 2nd ed. Totowa, New Jersey: Humana Press; 2006. pp. 329-341.
27. Silva AJ, Simpson EM, Takahashi JS, Lipp H-P, Nakanishi S, Wehner JM, et al. Mutant mice and neuroscience: recommendations concerning genetic background. Banbury Conference on genetic background in mice. Neuron 1997; 19:755-759.
28. Hough TA, Nolan PM, Tsipouri V, Toye AA, Gray IC, Goldsworthy M, et al. Novel phenotypes identified by plasma biochemical screening in the mouse. Mamm Genome 2002; 13:595-602.
29. Rogers DC, Fisher EM, Brown SD, Peters J, Hunter AJ, Martin JE. Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment. Mamm Genome 1997; 8:711-713.
30. Liu W, Saint DA. A new quantitative method of real time reverse transcription polymerase chain reaction assay based on simulation of polymerase chain reaction kinetics. Anal Biochem 2002; 302:52-59.
31. Phillips IR, Shephard EA, Mitani F, Rabin BR. Induction by phenobarbital of the mRNA for a specific variant of rat liver microsomal cytochrome P-450. Biochem J 1981; 196:839-851.
32. Dolphin CT, Janmohamed A, Smith RL, Shephard EA, Phillips IR. Missense mutation in flavin-containing mono-oxygenase 3 gene, FMO3, underlies fish-odour syndrome. Nat Gener 1997; 17:491-494.
33. Janmohamed A, Thaunsukon P, Shephard EA, Phillips IR. Expression of recombinant flavin-containing monooxygenases in a baculovirus/insect cell system. In: Phillips IR, Shephard EA, editors. Cytochrome P450 protocols. 2nd ed. Totowa, New Jersey: Humana Press; 2006. pp. 39-59.
34. Yoo SD, Holladay JW, Fincher TK, Dewey MJ. Rapid microsample analysis of imipramine and desipramine by reversed-phase high-performance liquid chromatography with ultraviolet detection. J Chromatogr B Biomed Appl 1995; 668:338-342.
35. Aitchison KJ, Jann MW, Zhao JH, Sakai T, Zaher H, Wolff K, et al. Clozapine pharmacokinetics and pharmacodynamics studied with Cyp1A2-null mice. J Psychopharmacol 2000; 14:353-359.
36. Nagy A. The kinetics of imipramine N-oxide in rats. Acta Pharmacol Toxicol 1978; 42:68-72.
37. Nagy A, Treiber L Quantitative determination of imipramine and desipramine in human blood plasma by direct densitometry of thin-layer chromatograms. J Pharm Pharmacol 1973; 25:599-603.
38. Nagy A, Hansen T. The kinetics of imipramine N-oxide in man. Acta Pharmacol Toxicol 1978; 42:58-67.
39. Zheng B, Mills AA, Bradley A. A system for rapid generation of coat color-tagged knockouts and defined chromosomal rearrangements in mice. Nucleic Acids Res 1999; 27:2354-2360.
40. Dolphin C, Shephard EA, Povey S, Palmer CN, Ziegler DM, Ayesh R, et al. Cloning, primary sequence, and chromosomal mapping of a human flavincontaining monooxygenase (FMO1). J Biol Chem 1991; 266: 12379-12385.
41. Phillips IR, Dolphin CT, Clair P, Hadley MR, Hutt AJ, McCombie RR, et al. The molecular biology of the flavin-containing monooxygenases of man. Chem Biol Interact 1995; 96:17-32.
42. Koukouritaki SB, Simpson P, Yeung CK, Rettie AE, Hines RN. Human hepatic flavin-containing monooxygenases 1 (FMO1) and 3 (FMO3) developmental expression. Pediatr Res 2002; 51:236-243.
43. Yeung CK, Lang DH, Thummel KE, Rettie AE. Immunoquantitation of FM01 in human liver, kidney, and intestine. Drug Metab Dispos 2000; 28: 1107-1111.
44. Dolphin CT, Beckett DJ, Janmohamed A, Cullingford TE, Smith RL, Shephard EA, Phillips IR. The flavin-containing monooxygenase 2 gene (FMO2) of humans, but not of other primates, encodes a truncated, nonfunctional protein. J Biol Chem 1998; 273:30599-30607.
45. Whetstine JR, Yueh M, McCarver DG, Williams DE, Park C, Kang JH, et al. Ethnic differences in human flavin-containing monooxygenase 2 (FMO2) polymorphisms: detection of expressed protein in African-Americans. Toxicol Appl Pharmacol 2000; 168:216-224.
46. Veeramah K, Thomas MG, Weale ME, Zeitlyn D, Tarekegn A, Bekele E, et al. The potentially deleterious functional variant flavin-containing monooxygenase 2* 1 is at high frequency throughout sub-Saharan Africa. Pharmacogenet Genomics 2008; 18:877-886.
47. Janmohamed A, Hernandez D, Phillips IR, Shephard EA. Cell-, tissue-, sex- and developmental stage-specific expression of mouse flavin-containing monooxygenases (Fmos). Biochem Pharmacol 2004; 68:73-83.
48. Lemoine A, Johann M, Cresteil T. Evidence for the presence of distinct flavin-containing monooxygenases in human tissues. Arch Biochem Biophys 1990; 276:336-342.
49. Nelson JC, Jatlow PI, Quinlan DM. Subjective complaints during desipramine treatment. Relative importance of plasma drug concentrations and the severity of depression. Arch Gen Psychiatry 1984; 41:55-59.
50. Rapp W, Noren MB, Pedersen F. Comparative trial of imipramine N-oxide and imipramine in the treatment of out-patients with depressive syndromes. Acta Psychiatr Scand 1973; 49:77-90.
51. Dolphin CT, Cullingford TE, Shephard EA, Smith RL, Phillips IR. Differential developmental and tissue-specific regulation of expression of the genes encoding three members of the flavin-containing monooxygenase family of man, FMO1, FMO3 and FM04. Eur J Biochem 1996; 235:683-689.
52. Christiansen J, Gram LF. Imipramine and its metabolites in human brain. J Pharm Pharmacol 1973; 25:604-608.
53. Koyama E, Kikuchi Y, Echizen H, Chiba K, Ishizaki T. Simultaneous high-performance liquid chromatography-electrochemical detection determination of imipramine, desipramine, their 2-hydroxylated metabolites, and imipramine N-oxide in human plasma and urine: preliminary application to oxidation pharmacogenetics. Ther Drug Monit 1993; 15:224-235.