Only low levels of exogenous N-acetyltransferase can be achieved in transgenic mice
Therapeutic and environmental aromatic amines and hydrazines are substrates for the arylamine N-acetyltransferases (NAT). In all, 10 transgenic lines containing either the human NAT1 or NAT2 transgene were developed using multiple promoters. The presence of the transgene was confirmed by determining...
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| Veröffentlicht in: | The pharmacogenomics journal 2005-01, Vol.5 (4), p.255-261 |
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| creator | Cao, W Chau, B Hunter, R Strnatka, D McQueen, C A Erickson, R P |
| description | Therapeutic and environmental aromatic amines and hydrazines are substrates for the arylamine N-acetyltransferases (NAT). In all, 10 transgenic lines containing either the human NAT1 or NAT2 transgene were developed using multiple promoters. The presence of the transgene was confirmed by determining copy number, mRNA and enzyme activity. Despite some lines having high copy numbers of the transgene, only modest or no increases in enzymatic activity could be found in a variety of tissues. The NAT1 transgene could not be bred to homozygosity. The cytomegalovirus (CMV)-promoted NAT1 transgene increased endogenous Nat1 mRNA levels in liver and had little effect on endogenous Nat2 mRNA levels. The presence of the CMV-promoted NAT2 transgene appeared to suppress endogenous hepatic Nat2 mRNA, but did not alter Nat1 mRNA levels. The failure to achieve high expression of any of the transgenes suggests that overexpression of NAT genes may have harmful effects during development. |
| doi_str_mv | 10.1038/sj.tpj.6500319 |
| format | Article |
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In all, 10 transgenic lines containing either the human NAT1 or NAT2 transgene were developed using multiple promoters. The presence of the transgene was confirmed by determining copy number, mRNA and enzyme activity. Despite some lines having high copy numbers of the transgene, only modest or no increases in enzymatic activity could be found in a variety of tissues. The NAT1 transgene could not be bred to homozygosity. The cytomegalovirus (CMV)-promoted NAT1 transgene increased endogenous Nat1 mRNA levels in liver and had little effect on endogenous Nat2 mRNA levels. The presence of the CMV-promoted NAT2 transgene appeared to suppress endogenous hepatic Nat2 mRNA, but did not alter Nat1 mRNA levels. The failure to achieve high expression of any of the transgenes suggests that overexpression of NAT genes may have harmful effects during development.</description><identifier>ISSN: 1470-269X</identifier><identifier>EISSN: 1473-1150</identifier><identifier>DOI: 10.1038/sj.tpj.6500319</identifier><identifier>PMID: 16041393</identifier><language>eng</language><publisher>United States: Nature Publishing Group</publisher><subject>Acetyltransferase ; Amines ; Animals ; Arylamine N-Acetyltransferase - genetics ; Arylamine N-Acetyltransferase - metabolism ; Cloning, Molecular ; Copy number ; Cytomegalovirus ; Cytomegalovirus - genetics ; Enzymatic activity ; Humans ; Isoenzymes ; Liver - enzymology ; Mice ; Mice, Transgenic ; mRNA ; N-acetyltransferase 1 ; N-Acetyltransferase 2 ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Transgenes ; Transgenes - genetics ; Transgenic mice</subject><ispartof>The pharmacogenomics journal, 2005-01, Vol.5 (4), p.255-261</ispartof><rights>COPYRIGHT 2005 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group 2005</rights><rights>Nature Publishing Group 2005.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-620901b65bb11226c3eecc0a2cb60e1678fbcf2648c3c4de7ff558ac24fa2a693</citedby><cites>FETCH-LOGICAL-c427t-620901b65bb11226c3eecc0a2cb60e1678fbcf2648c3c4de7ff558ac24fa2a693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16041393$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cao, W</creatorcontrib><creatorcontrib>Chau, B</creatorcontrib><creatorcontrib>Hunter, R</creatorcontrib><creatorcontrib>Strnatka, D</creatorcontrib><creatorcontrib>McQueen, C A</creatorcontrib><creatorcontrib>Erickson, R P</creatorcontrib><title>Only low levels of exogenous N-acetyltransferase can be achieved in transgenic mice</title><title>The pharmacogenomics journal</title><addtitle>Pharmacogenomics J</addtitle><description>Therapeutic and environmental aromatic amines and hydrazines are substrates for the arylamine N-acetyltransferases (NAT). In all, 10 transgenic lines containing either the human NAT1 or NAT2 transgene were developed using multiple promoters. The presence of the transgene was confirmed by determining copy number, mRNA and enzyme activity. Despite some lines having high copy numbers of the transgene, only modest or no increases in enzymatic activity could be found in a variety of tissues. The NAT1 transgene could not be bred to homozygosity. The cytomegalovirus (CMV)-promoted NAT1 transgene increased endogenous Nat1 mRNA levels in liver and had little effect on endogenous Nat2 mRNA levels. The presence of the CMV-promoted NAT2 transgene appeared to suppress endogenous hepatic Nat2 mRNA, but did not alter Nat1 mRNA levels. The failure to achieve high expression of any of the transgenes suggests that overexpression of NAT genes may have harmful effects during development.</description><subject>Acetyltransferase</subject><subject>Amines</subject><subject>Animals</subject><subject>Arylamine N-Acetyltransferase - genetics</subject><subject>Arylamine N-Acetyltransferase - metabolism</subject><subject>Cloning, Molecular</subject><subject>Copy number</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus - genetics</subject><subject>Enzymatic activity</subject><subject>Humans</subject><subject>Isoenzymes</subject><subject>Liver - enzymology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>mRNA</subject><subject>N-acetyltransferase 1</subject><subject>N-Acetyltransferase 2</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Transgenes</subject><subject>Transgenes - genetics</subject><subject>Transgenic mice</subject><issn>1470-269X</issn><issn>1473-1150</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kcFrFTEQxoNYbK1ePUpQ8LbPmSSbzR5LqVYo9lAFbyGbN6m75CXPzT7r--9N2wcFQXKYkPl9k2_4GHuDsEKQ5mOZVst2WukWQGL_jJ2g6mSD2MLzhzs0Qvc_jtnLUiYA1NiZF-wYNSiUvTxhN9cp7nnMdzzSb4qF58DpT76llHeFf22cp2Ufl9mlEmh2hbh3iQ_Enf85VsWaj4k_tKtk9HwzenrFjoKLhV4f6in7_uni2_llc3X9-cv52VXjleiWRgvoAQfdDgOiENpLIu_BCT9oINSdCYMPQivjpVdr6kJoW-O8UMEJp3t5yj48zt3O-deOymI3Y_EUo0tU3VttoAOj2gq-_wec8m5O1Zut41H3PQhRqXf_pYQB3Sp1_-fqEbp1keyYQq7L-3rWVFfPicJY38_Q9EJ3ooUngZ9zKTMFu53HjZv3FsHeR2jLZGuE9hBhFbw92NgNG1o_4YfM5F-AY5bl</recordid><startdate>20050101</startdate><enddate>20050101</enddate><creator>Cao, W</creator><creator>Chau, B</creator><creator>Hunter, R</creator><creator>Strnatka, D</creator><creator>McQueen, C A</creator><creator>Erickson, R P</creator><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20050101</creationdate><title>Only low levels of exogenous N-acetyltransferase can be achieved in transgenic mice</title><author>Cao, W ; 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| subjects | Acetyltransferase Amines Animals Arylamine N-Acetyltransferase - genetics Arylamine N-Acetyltransferase - metabolism Cloning, Molecular Copy number Cytomegalovirus Cytomegalovirus - genetics Enzymatic activity Humans Isoenzymes Liver - enzymology Mice Mice, Transgenic mRNA N-acetyltransferase 1 N-Acetyltransferase 2 Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism Transgenes Transgenes - genetics Transgenic mice |
| title | Only low levels of exogenous N-acetyltransferase can be achieved in transgenic mice |
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