Strain Name:

STOCK Dbttm1Geh Tg(Cebpb-tTA)5Bjd Tg(tetO-DBT)A1Geh/J

Stock Number:

006999

Availability:

On Hold

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Description

Strain Information

Former Names STOCK Dbttm1Geh Tg(tTALap)5Bjd Tg(tetO-DBT)A1Geh/J    (Changed: 30-SEP-11 )
STOCK Dbttm1Geh Tg(tTALap)5Bjd Tg(tetO-DBT*)A1Geh/J    (Changed: 11-MAY-07 )
Type Mutant Stock; Targeted Mutation; Transgenic;
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Specieslaboratory mouse
Generation?+F3p
Generation Definitions
 
Donating InvestigatorDr. Gregg Homanics,   University of Pittsburgh

Description
Mice homozygous for the Dbt (E2) targeted mutation and carrying both the LAP-tTA and TRE-E2 transgenes are viable and fertile. The E2-targeted mutation leads to absence of branched-chain keto acid dehydrogenase (BCKDH) activity and E2 protein in liver tissue, but this absence is rescued by the two transgenes: liver-directed expression of the modified human BCKDH E2 subunit from the complimentary "Tet-off" transgenes abrogates the severity of Maple Syrup Urine Disease (MSUD) phenotype observed in E2-deficient single mutant mice. Triple mutant mice are a model for intermediate MSUD (iMSUD); BCKDH activity is only 5-6% of that found in wildtype mice. This low level of BCKDH activity is sufficient to allow survival, but insufficient to normalize circulating branched chain amino acids levels. Because these mice have near normal amounts of E2 protein, but only 5-6% of normal BCKDH enzyme activity, it is probable that the c-myc tag at the carboxy-terminus of the human E2 transgene interferes with enzymatic activity. The donating investigator reports that addition of the tetracycline analog doxycycline does not affect MSUD phenotype rescue. These mutant mice may be useful in studying metabolic disease, biochemistry, and both the complete/classic and intermediate forms of Maple Syrup Urine Disease.

Development
The mutant allele of branched-chain keto acid dehydrogenase E2 subunit (Dbt gene) was created by Dr. Gregg Homanics (University of Pittsburgh) using a targeting vector designed to replace part of exon 4 and all of exon 5 with a PGKneo cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were microinjected into C57BL/6J blastocysts. Chimeric mice were bred to C57BL/6J to generate heterozygous mice. Heterozygotes were then bred to LAP-tTA transgenic mice on a mixed (NMRI outbred;FVB;C57BL/6J) background. These mice were created by Dr. Hermann Bujard (Universitat Heidelberg) to express tetracycline-controlled transactivator (tTA) under control of the rat liver-enriched activator protein promoter. The TRE-E2 (or tetO-DBT*) transgene, also created by Dr. Gregg Homanics, contains a tetracycline response element and minimal human CMV promoter controlling a human E2 subunit (DBT gene) cDNA which has been modified to contain a 4x alanine linker followed by a c-myc epitope tag at the carboxy terminus. After injection of the transgene into C57BL/6J embryos, founder line A mice were bred with E2-deficient, LAP-tTA double mutant mice to generate this triple mutant strain.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Tg(Cebpb-tTA)5Bjd allele
003563   B6.Cg-Tg(Cebpb-tTA)5Bjd/J
016970   STOCK Tg(tetO-HCV)1Mlch/Mmjax
View Strains carrying   Tg(Cebpb-tTA)5Bjd     (2 strains)

Strains carrying other alleles of tTA
008079   129S-Ppargtm2Yba/J
016198   129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ
011008   B6.129P2(Cg)-Gt(ROSA)26Sortm1(tTA)Roos/J
009602   B6.129S4(Cg)-Kcnn2tm2Jpad/J
009603   B6.129S4-Kcnn3tm1Jpad/J
008227   B6.129S4-Ppargtm3Yba/J
016868   B6.Cg-Ssttm1.2(tTA2)Hze/J
007004   B6.Cg-Tg(Camk2a-tTA)1Mmay/DboJ
003767   B6.Cg-Tg(Eno2tTA)5021Nes/J
003763   B6.Cg-Tg(Eno2tTA)5030Nes/J
018306   B6.Cg-Tg(Fos-tTA,Fos-EGFP*)1Mmay/J
005964   B6.Cg-Tg(GFAP-tTA)110Pop/J
002618   B6.Cg-Tg(MMTVtTA)1Mam/J
008284   B6.Cg-Tg(Scg2-tTA)1Jt/J
023970   B6.Cg-Tg(Sirpa-tTA)AUmri/J
023971   B6.Cg-Tg(Sirpa-tTA)SUmri/J
006361   B6.Cg-Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/J
017722   B6.Cg-Tg(Tal1-tTA)19Dgt/J
017754   B6;129-Omptm1(tTA)Gogo/J
007585   B6;129S4-Npytm2Rpa/J
002709   B6;C3-Tg(TettTALuc)1Dgs/J
003010   B6;CBA-Tg(Camk2a-tTA)1Mmay/J
008344   B6;DBA-Tg(Fos-tTA,Fos-EGFP*)1Mmay Tg(tetO-lacZ,tTA*)1Mmay/J
010573   B6;SJL-Tg(Prl-tTA)6-5Jek/J
008082   B6;SJL-Tg(Tagln-tTA)1Mrab Tg(tetO-Mcpt1)1Mrab/J
008603   C.129P2(B6)-Gt(ROSA)26Sortm1(tTA)Roos/J
010712   C57BL/6-Tg(Camk2a-tTA)1Stl/J
013585   FVB-Tg(Cdh5-tTA)D5Lbjn/J
005625   FVB-Tg(Pcp2-tTA)3Horr/J
003170   FVB.Cg-Tg(Myh6-tTA)6Smbf/J
006209   FVB.Cg-Tg(Tal1-tTA)19Dgt/J
005942   FVB/N-Tg(Pf4-tTA/VP16)42Kra/J
004937   NOD.Cg-Tg(Ins2-tTA)1Doi/DoiJ
008335   STOCK Foxa2tm1.1(rtTa)Moon/J
008600   STOCK Gt(ROSA)26Sortm1(tTA)Roos/J
024108   STOCK Igs7tm93.1(tetO-GCaMP6f)Hze Tg(Camk2a-tTA)1Mmay/J
005701   STOCK Pdx1tm1Macd/J
014092   STOCK Tg(ACTB-tTA2,-MAPT/lacZ)1Luo/J
003271   STOCK Tg(CMV-tTA)3Bjd/J
024854   STOCK Tg(Camk2a-tTA)1Mmay Tg(tetO-MAPT*P301L)#Kha/J
018124   STOCK Tg(Prnp-tTA)F959Sbp/J
009606   STOCK Tg(Six2-EGFP/cre)1Amc/J
003275   STOCK Tg(tetL)1Bjd/J
003274   STOCK Tg(tetNZL)2Bjd/J
View Strains carrying other alleles of tTA     (44 strains)

Strains carrying other alleles of tetO
008079   129S-Ppargtm2Yba/J
016178   B6(Cg)-Tg(tetO-Cry2)3Jt/J
016176   B6(Cg)-Tg(tetO-Per2)2Jt/J
023757   B6(Cg)-Tg(tetO-tetX,lacZ)1Gogo/UmriJ
009602   B6.129S4(Cg)-Kcnn2tm2Jpad/J
009603   B6.129S4-Kcnn3tm1Jpad/J
023910   B6.Cg-Col1a1tm1(tetO-Lin28a)Gqda/J
023911   B6.Cg-Col1a1tm2(tetO-LIN28B)Gqda/J
023912   B6.Cg-Col1a1tm3(tetO-Mirlet7g/Mir21)Gqda/J
017983   B6.Cg-Col1a1tm9(tetO-Dnmt3b_i1)Jae Gt(ROSA)26Sortm1(rtTA*M2)Jae/J
014588   B6.Cg-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm6(tetO-MSI2)Jae/J
023749   B6.Cg-Gt(ROSA)26Sortm1(rtTA*M2)Jae Tg(tetO-Pou5f1,-Sox2,-Klf4,-Myc)1Srn/J
014648   B6.Cg-Gt(ROSA)26Sortm37(H1/tetO-RNAi:Taz)Arte/ZkhuJ
006361   B6.Cg-Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/J
016998   B6.Cg-Tg(TetO-Axin1,EGFP)TA6Cos/J
003762   B6.Cg-Tg(tetFosb)4468Nes/J
007051   B6.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax
007052   B6.Cg-Tg(tetO-APPSwInd)107Dbo/Mmjax
007049   B6.Cg-Tg(tetO-APPSwInd)885Dbo/Mmjax
007618   B6.Cg-Tg(tetO-Arntl)1Jt/J
017555   B6.Cg-Tg(tetO-CALY)5Cber/J
024114   B6.Cg-Tg(tetO-CHRM4*)2Blr/J
008277   B6.Cg-Tg(tetO-Clockm1Jt)CL57Jt/J
008468   B6.Cg-Tg(tetO-DTA)1Gfi/J
017791   B6.Cg-Tg(tetO-Hamp)2181Nca/J
009344   B6.Cg-Tg(tetO-Ifng)184Pop/J
009136   B6.Cg-Tg(tetO-Kcnj2,lacZ)1Gogo/J
013583   B6.Cg-Tg(tetO-LRRK2)C7874Cai/J
020652   B6.Cg-Tg(tetO-Mif)279Aren/J
017331   B6.Cg-Tg(tetO-Ppp3ca*)11255Kndl/J
017332   B6.Cg-Tg(tetO-Ppp3ca*)13967Kndl/J
017330   B6.Cg-Tg(tetO-TAg*)175Kndl/J
006234   B6.Cg-Tg(tetO-cre)1Jaw/J
005738   B6.FVB-Tg(tetO-EGFP,-Tgfbr2)8Mcle/J
021025   B6;129-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm1(tetO-cre)Haho/J
006911   B6;129-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm2(tetO-Pou5f1)Jae/J
011001   B6;129S4-Col1a1tm1(tetO-Pou5f1,-Klf4,-Sox2,-Myc)Hoch/J
016836   B6;129S4-Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm7(tetO-HIST1H2BJ/GFP)Jae/J
012433   B6;C3-Tg(ACTA1-rtTA,tetO-cre)102Monk/J
002709   B6;C3-Tg(TettTALuc)1Dgs/J
023598   B6;C3-Tg(tetO-AIMP2)630Tmd/J
023642   B6;C3-Tg(tetO-AIMP2)634Tmd/J
016841   B6;C3-Tg(tetO-TARDBP)12Vle/J
014650   B6;C3-Tg(tetO-TARDBP*)4Vle/J
012450   B6;D2-Tg(tetO-SNCA)1Cai/J
008344   B6;DBA-Tg(Fos-tTA,Fos-EGFP*)1Mmay Tg(tetO-lacZ,tTA*)1Mmay/J
024742   B6;DBA-Tg(tetO-GCaMP6s)2Niell/J
024088   B6;FVB-Tg(tetO-AML1/ETO)8Dzh/J
008082   B6;SJL-Tg(Tagln-tTA)1Mrab Tg(tetO-Mcpt1)1Mrab/J
010575   B6;SJL-Tg(tetO-Egfr*)2-9Jek/J
010577   B6;SJL-Tg(tetO-Erbb2*)8-4Jek/J
002621   B6;SJL-Tg(tetop-lacZ)2Mam/J
006004   B6C3-Tg(tetO-APPSwInd)885Dbo/Mmjax
016976   B6C3-Tg(tetO-SNCA*A53T)33Vle/J
018913   B6N.Cg-Tg(tetO-GFP,-lacZ)G3Rsp/J
006244   C.Cg-Tg(tetO-cre)1Jaw/J
017719   C3HeB/FeJ-Tg(tetO-TAg)1Efr/J
017955   C57BL/6-Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan/J
025487   C57BL/6-Tg(tetO-Aimp1)29872Mcla/J
005706   C57BL/6-Tg(tetO-CDK5R1/GFP)337Lht/J
006618   C57BL/6-Tg(tetO-COX8A/EYFP)1Ksn/J
017613   C57BL/6-Tg(tetO-Cdkn1b)1Scpr/J
013729   C57BL/6-Tg(tetO-EDN1,-lacZ)9Mhus/J
016260   C57BL/6-Tg(tetO-Fbxl21)38Jt/J
016179   C57BL/6-Tg(tetO-Fbxl21*)11Jt/J
010713   C57BL/6-Tg(tetO-GFP/tetX)5696Stl/J
013728   C57BL/6-Tg(tetO-NOS2,-lacZ)240iMhus/J
016181   C57BL/6-Tg(tetO-Nr1d1)1Schb/J
016581   C57BL/6J-Tg(tetO-Btrc*)1Jt/J
008278   C57BL/6J-Tg(tetO-Clock)1Jt/J
024898   C57BL/6J-Tg(tetO-EGFP/Rpl10a)5aReij/J
016580   C57BL/6J-Tg(tetO-Usf1)2Jt/J
021065   FVB(C)-Tg(tetO-Npc1/YFP)1Mps/J
017542   FVB-Tg(Myh6/tetO-ATP2B4)1Jmol/J
016571   FVB-Tg(Myh6/tetO-Gata6)2Jmol/J
014155   FVB-Tg(Myh6/tetO-Itpr1)22.3Jmol/J
014153   FVB-Tg(Myh6/tetO-Itpr2)3.11Jmol/J
014154   FVB-Tg(Myh6/tetO-Itpr2)4.9Jmol/J
012684   FVB-Tg(Myh6/tetO-POSTN)22.1Jmol/J
010580   FVB-Tg(Myh6/tetO-PRKCA*)1Jmk/J
013156   FVB-Tg(tetO-CDK5R1*)1Vln/J
013777   FVB-Tg(tetO-Cacna1g)1Jmol/J
013778   FVB-Tg(tetO-Cacnb2)1Jmol/J
013779   FVB-Tg(tetO-Cacnb2)2Jmol/J
013780   FVB-Tg(tetO-Cib1)1Jmol/J
010578   FVB-Tg(tetO-Dusp6)1Jmol/J
017333   FVB-Tg(tetO-Gnai2*,-lacZ)382Kndl/J
008685   FVB-Tg(tetO-Kdr*)4377.5Rwng/J
023397   FVB-Tg(tetO-Lmnb1)AF1Yfu/J
015815   FVB-Tg(tetO-MAPT*P301L)#Kha/JlwsJ
008695   FVB-Tg(tetO-MET)23Rwng/J
012387   FVB-Tg(tetO-Ppargc1a)1Dpk/J
012385   FVB-Tg(tetO-Ppargc1b)7Dpk/J
022979   FVB-Tg(tetO-Thbs4)17.7Jmol/J
006439   FVB-Tg(tetO/CMV-KRAS*G12C)9.1Msmi/J
019038   FVB.Cg-Tg(tetO-GLI1)10Rup/Mmjax
019039   FVB.Cg-Tg(tetO-KLF4)32831Rup/Mmjax
008244   FVB.Cg-Tg(tetO-cre)1Jaw/J
012459   FVB/N-Tg(Myh6*/tetO-Capn1)L2Gwd/J
005941   FVB/N-Tg(tetO-Aurkb,lacZ)41Kra/J
006202   FVB/N-Tg(tetO-BCR/ABL1)2Dgt/J
014547   FVB/N-Tg(tetO-Fasl)BDepa/J
025672   FVB/N-Tg(tetO-Fgfr2b/Igh)1.3Jaw/J
019376   FVB/N-Tg(tetO-MYC)36aBop/J
026278   FVB/N-Tg(tetO-Ube3a*1)1Svd/J
026279   FVB/N-Tg(tetO-Ube3a*2)884Svd/J
022938   FVB/N-Tg(tetO-Wnt5a)17Rva/J
003315   FVB/N-Tg(tetORo1-lacZ)3Conk/J
005076   NOD.Cg-Tg(tetO-EGFP/FADD)1Doi/DoiJ
011004   STOCK Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm3(tetO-Pou5f1,-Sox2,-Klf4,-Myc)Jae/J
011011   STOCK Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm4(tetO-Pou5f1,-Sox2,-Klf4,-Myc)Jae/J
011013   STOCK Gt(ROSA)26Sortm1(rtTA*M2)Jae Col1a1tm5(tetO-Pou5f1,-Klf4,-Myc)Jae/J
017596   STOCK Gt(ROSA)26Sortm1.1(rtTA,EGFP)Nagy Tg(SMN2)89Ahmb Smn1tm1Msd Tg(SMN2*delta7)4299Ahmb Tg(tetO-SMN2,-luc)#aAhmb/J
017597   STOCK Gt(ROSA)26Sortm1.1(rtTA,EGFP)Nagy Tg(SMN2)89Ahmb Smn1tm1Msd Tg(SMN2*delta7)4299Ahmb Tg(tetO-SMN2,-luc)#bAhmb/J
025671   STOCK Gt(ROSA)26Sortm1.1(rtTA,EGFP)Nagy Tg(tetO-Fgf10)1Jaw/SpdlJ
024854   STOCK Tg(Camk2a-tTA)1Mmay Tg(tetO-MAPT*P301L)#Kha/J
008755   STOCK Tg(Ins2-rtTA)2Efr Tg(teto-DTA)1Gfi/J
012477   STOCK Tg(Myh6*/tetO-GCaMP2)1Mik/J
016572   STOCK Tg(Myh6/tetO-Gata4)1Jmol/J
014544   STOCK Tg(tetO-ABL1*P242E*P249E)CPdav/J
014093   STOCK Tg(tetO-CHRM3*)1Blr/J
008790   STOCK Tg(tetO-DISC1*)1001Plet/J
008168   STOCK Tg(tetO-DTA)1Gfi/J
017755   STOCK Tg(tetO-GCAMP2)12iRyu/J
024509   STOCK Tg(tetO-Gata6)1Abl/J
016970   STOCK Tg(tetO-HCV)1Mlch/Mmjax
005104   STOCK Tg(tetO-HIST1H2BJ/GFP)47Efu/J
005699   STOCK Tg(tetO-Ipf1,EGFP)956.6Macd/J
005728   STOCK Tg(tetO-Ipf1,lacZ)958.1Macd/J
012441   STOCK Tg(tetO-LRRK2*G2019S)E3Cai/J
017918   STOCK Tg(tetO-MAML1*/EGFP)2Akar/J
017599   STOCK Tg(tetO-SMN2,-luc)#aAhmb/J
017600   STOCK Tg(tetO-SMN2,-luc)#bAhmb/J
012442   STOCK Tg(tetO-SNCA*A53T)E2Cai/J
006224   STOCK Tg(tetO-cre)1Jaw/J
017906   STOCK Tg(tetO-hop/EGFP,-COP4/mCherry)6Kftnk/J
012345   STOCK Tg(tetO-tdTomato,-Syp/EGFP*)1.1Luo/J
012449   STOCK Tg(teto-LRRK2)C7874Cai/J
View Strains carrying other alleles of tetO     (138 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Maple Syrup Urine Disease; MSUD
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Dbttm1Geh/Dbttm1Geh Tg(tetO-DBT)A1Geh/0 Tg(Cebpb-tTA)5Bjd/0

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB * NMRI
  • mortality/aging
  • postnatal lethality
    • approximately 4% of pups surviving to weaning have this genotype, compared to a theoretical survival rate or 14%, indicating partial rescue of the Dbttm1Geh phenotype   (MGI Ref ID J:119973)
  • premature death
    • transgenic mice survival is only ~16 weeks, when mice become moribund and are sacrificed   (MGI Ref ID J:119973)
  • homeostasis/metabolism phenotype
  • abnormal circulating amino acid level
    • blood levels of alanine, glutamate, and glutamine are reduced compared to controls, but greater than in Dbttm1Geh homozygous mice   (MGI Ref ID J:119973)
    • BCAA/alanine (BCAA -branched-chain amino acids - leucine + isoleucine + valine) values are intermediate between controls and Dbt-null mice between 4-7 weeks of age   (MGI Ref ID J:119973)
  • abnormal enzyme/coenzyme activity
    • levels of branched-chain keto acid dehydrogenase (BCKDH) activity are only 5-6% of controls levels, despite nearly equal protein levels, indicating suboptimal BCKDH activity of protein assembled with human E2   (MGI Ref ID J:119973)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Metabolism Research
Enzyme Deficiency

Research Tools
Cardiovascular Research
      Tetop Tet System
Metabolism Research
Tet Expression Systems
      tTA/rtTA Expressing Strains
      tTA/rtTA Responsive Strains

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Dbttm1Geh
Allele Name targeted mutation 1, Gregg E Homanics
Allele Type Targeted (Null/Knockout)
Common Name(s) E2 KO;
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Site of ExpressionThe targeted mutation leads to absence of branched-chain keto acid dehydrogenase activity and E2 protein in liver tissue.
Gene Symbol and Name Dbt, dihydrolipoamide branched chain transacylase E2
Chromosome 3
Gene Common Name(s) BCATE2; BCKAD E2; BCKAD-E2; BCKADE2; D3Wsu60e; DNA segment, Chr 3, Wayne State University 60, expressed; E2; E2B; dihydrolipoyl transacylase; dihydrolipoyllysine-residue (2-methylpropanoyl)transferase;
Molecular Note A targeting vector was used to replace part of exon 4 and all of exon 5 with a PGKneo cassette.Southern blot and immunohistochemical analyses verify the absence of wild-type E2 transcripts and lack of E2 protein detection in homozygotes. [MGI Ref ID J:119973]
 
Allele Symbol Tg(Cebpb-tTA)5Bjd
Allele Name transgene insertion 5, Hermann Bujard
Allele Type Transgenic (Transactivator)
Common Name(s) LAP-tTA; Tg(tTALap)5Uh; g(tTALap)5Bjd;
Mutation Made ByDr. Hermann Bujard,   Universit┐t Heidelberg
Strain of OriginNMRI
Site of ExpressionExpresses tTA at high levels in the liver; see Stock No. 003563
Expressed Gene tTA, tetracycline-controlled transactivator, E. coli
The tetracycline-resistance gene (TetR), arose from chemically mutated Escherichia coli genome which was screened for tetracycline dependence (Gossen and Bujard, 1992). TetR was fused at the C-terminus with the viral co-activator, virion protein 16 of the herpes simplex virus (VP-16). The tetracycline-inhibitable transcription factor is a component of a bigenic system that allows doxycycline (a tetracycline analog) regulatable expression of genes that are under the direction of the tetracycline responsive promoter (TetOp)promoter.
Promoter Cebpb, CCAAT/enhancer binding protein (C/EBP), beta, rat
General Note Transgenic mice on a C57BL/6J background are viable and fertile, and express tTA in the liver.
Molecular Note This transgene contains the gene encoding the tetracycline regulated transactivator protein (tTA) driven by the rat Cebpb promoter (previously called liver-enriched activator protein). [MGI Ref ID J:93000]
 
 
 
Allele Symbol Tg(tetO-DBT)A1Geh
Allele Name transgene insertion A1, Gregg E Homanics
Allele Type Transgenic (Hypomorph, Inducible, Inserted expressed sequence)
Common Name(s) TRE-E2 (line A);
Strain of OriginC57BL/6J
Site of ExpressionExpresses tTA at high levels in the liver; see Stock No. 003563
Expressed Gene DBT, dihydrolipoamide branched chain transacylase E2, human
Expressed Gene tTA, tetracycline-controlled transactivator, E. coli
The tetracycline-resistance gene (TetR), arose from chemically mutated Escherichia coli genome which was screened for tetracycline dependence (Gossen and Bujard, 1992). TetR was fused at the C-terminus with the viral co-activator, virion protein 16 of the herpes simplex virus (VP-16). The tetracycline-inhibitable transcription factor is a component of a bigenic system that allows doxycycline (a tetracycline analog) regulatable expression of genes that are under the direction of the tetracycline responsive promoter (TetOp)promoter.
Promoter tetO, tet operator,
Molecular Note The TRE-E2 (or tetO-DBT) transgene contains a tetracycline response element and minimal human CMV promoter controlling a human E2 subunit (DBT gene) cDNA which has been modified to contain a 4x alanine linker followed by a c-myc epitope tag at the carboxy terminus to facilitate detection. Levels of the human E2 protein are approximately equal to mouse E2 protein in livers of control mice. However, when crossed to animals that express a transgene encoding the tetracycline regulated transactivator protein (Tg(tTALap)5Bjd) and are homozygous for a knockout allele of mouse E2 (Dbttm1Geh) are treated with doxycycline, the E2 protein levels correlate with only ~5-6% of normal branched-chain keto acid dehydrogenase (BCKDH) activity. It is one hypothesis that addition of the c-myc tag interferes with BCKDH subunit assembly (ie. interaction the human E2 subunit with mouse E1 and E3 complexes), thus reducing enzymatic activity. [MGI Ref ID J:119973]
 
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Dbttm1Geh, Separated PCR
Dbttm1Geh, Standard PCR
Tg(tTA),

MELT


Tg(tTA),

Probe


Tg(tTA), QPCR
Tg(tTA), Standard PCR
Tg(tetO-DBT)A1Geh, QPCR
Tg(tetO-DBT)A1Geh, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Homanics GE; Skvorak K; Ferguson C; Watkins S; Paul HS. 2006. Production and characterization of murine models of classic and intermediate maple syrup urine disease. BMC Med Genet 7:33. [PubMed: 16579849]  [MGI Ref ID J:119973]

Additional References

Dbttm1Geh related

Skvorak KJ; Hager EJ; Arning E; Bottiglieri T; Paul HS; Strom SC; Homanics GE; Sun Q; Jansen EE; Jakobs C; Zinnanti WJ; Gibson KM. 2009. Hepatocyte transplantation (HTx) corrects selected neurometabolic abnormalities in murine intermediate maple syrup urine disease (iMSUD). Biochim Biophys Acta 1792(10):1004-10. [PubMed: 19699299]  [MGI Ref ID J:164850]

Tg(Cebpb-tTA)5Bjd related

Beer S; Komatsubara K; Bellovin DI; Kurobe M; Sylvester K; Felsher DW. 2008. Hepatotoxin-induced changes in the adult murine liver promote MYC-induced tumorigenesis. PLoS ONE 3(6):e2493. [PubMed: 18560566]  [MGI Ref ID J:139884]

Beer S; Zetterberg A; Ihrie RA; McTaggart RA; Yang Q; Bradon N; Arvanitis C; Attardi LD; Feng S; Ruebner B; Cardiff RD; Felsher DW. 2004. Developmental Context Determines Latency of MYC-Induced Tumorigenesis. PLoS Biol 2(11):E332. [PubMed: 15455033]  [MGI Ref ID J:93372]

Cairo S; Armengol C; De Reynies A; Wei Y; Thomas E; Renard CA; Goga A; Balakrishnan A; Semeraro M; Gresh L; Pontoglio M; Strick-Marchand H; Levillayer F; Nouet Y; Rickman D; Gauthier F; Branchereau S; Brugieres L; Laithier V; Bouvier R; Boman F; Basso G;Michiels JF; Hofman P; Arbez-Gindre F; Jouan H; Rousselet-Chapeau MC; Berrebi D; Marcellin L; Plenat F; Zachar D; Joubert M; Selves J; Pasquier D; Bioulac-Sage P; Grotzer M; Childs M; Fabre M; Buendia MA. 2008. Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer. Cancer Cell 14(6):471-84. [PubMed: 19061838]  [MGI Ref ID J:142029]

Cao Z; Fan-Minogue H; Bellovin DI; Yevtodiyenko A; Arzeno J; Yang Q; Gambhir SS; Felsher DW. 2011. MYC Phosphorylation, Activation, and Tumorigenic Potential in Hepatocellular Carcinoma Are Regulated by HMG-CoA Reductase. Cancer Res 71(6):2286-97. [PubMed: 21262914]  [MGI Ref ID J:170758]

Carpenter B; Lin Y; Stoll S; Raffai RL; McCuskey R; Wang R. 2005. VEGF is crucial for the hepatic vascular development required for lipoprotein uptake. Development 132(14):3293-303. [PubMed: 15944181]  [MGI Ref ID J:100427]

Chow EK; Zhang XQ; Chen M; Lam R; Robinson E; Huang H; Schaffer D; Osawa E; Goga A; Ho D. 2011. Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment. Sci Transl Med 3(73):73ra21. [PubMed: 21389265]  [MGI Ref ID J:170992]

Dickins RA; McJunkin K; Hernando E; Premsrirut PK; Krizhanovsky V; Burgess DJ; Kim SY; Cordon-Cardo C; Zender L; Hannon GJ; Lowe SW. 2007. Tissue-specific and reversible RNA interference in transgenic mice. Nat Genet 39(7):914-21. [PubMed: 17572676]  [MGI Ref ID J:123006]

Goga A; Yang D; Tward AD; Morgan DO; Bishop JM. 2007. Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC. Nat Med 13(7):820-7. [PubMed: 17589519]  [MGI Ref ID J:125802]

Hasan MT; Schonig K; Berger S; Graewe W; Bujard H. 2001. Long-term, noninvasive imaging of regulated gene expression in living mice. Genesis 29(3):116-22. [PubMed: 11252052]  [MGI Ref ID J:127660]

Hasenfuss SC; Bakiri L; Thomsen MK; Hamacher R; Wagner EF. 2014. Activator Protein 1 transcription factor Fos-related antigen 1 (Fra-1) is dispensable for murine liver fibrosis, but modulates xenobiotic metabolism. Hepatology 59(1):261-73. [PubMed: 23703832]  [MGI Ref ID J:213764]

Hasenfuss SC; Bakiri L; Thomsen MK; Williams EG; Auwerx J; Wagner EF. 2014. Regulation of steatohepatitis and PPARgamma signaling by distinct AP-1 dimers. Cell Metab 19(1):84-95. [PubMed: 24411941]  [MGI Ref ID J:210545]

Hsu SH; Wang B; Kota J; Yu J; Costinean S; Kutay H; Yu L; Bai S; La Perle K; Chivukula RR; Mao H; Wei M; Clark KR; Mendell JR; Caligiuri MA; Jacob ST; Mendell JT; Ghoshal K. 2012. Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. J Clin Invest 122(8):2871-83. [PubMed: 22820288]  [MGI Ref ID J:190067]

Hu S; Balakrishnan A; Bok RA; Anderton B; Larson PE; Nelson SJ; Kurhanewicz J; Vigneron DB; Goga A. 2011. 13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression. Cell Metab 14(1):131-42. [PubMed: 21723511]  [MGI Ref ID J:176076]

Ivanovska I; Zhang C; Liu AM; Wong KF; Lee NP; Lewis P; Philippar U; Bansal D; Buser C; Scott M; Mao M; Poon RT; Fan ST; Cleary MA; Luk JM; Dai H. 2011. Gene signatures derived from a c-MET-driven liver cancer mouse model predict survival of patients with hepatocellular carcinoma. PLoS One 6(9):e24582. [PubMed: 21949730]  [MGI Ref ID J:177679]

Kim A; Joseph S; Khan A; Epstein CJ; Sobel R; Huang TT. 2010. Enhanced expression of mitochondrial superoxide dismutase leads to prolonged in vivo cell cycle progression and up-regulation of mitochondrial thioredoxin. Free Radic Biol Med 48(11):1501-12. [PubMed: 20188820]  [MGI Ref ID J:160351]

Kistner A; Gossen M; Zimmermann F; Jerecic J; Ullmer C; Lubbert H; Bujard H. 1996. Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc Natl Acad Sci U S A 93(20):10933-8. [PubMed: 8855286]  [MGI Ref ID J:93000]

Kornmann B; Schaad O; Bujard H; Takahashi JS; Schibler U. 2007. System-driven and oscillator-dependent circadian transcription in mice with a conditionally active liver clock. PLoS Biol 5(2):e34. [PubMed: 17298173]  [MGI Ref ID J:141590]

Kota J; Chivukula RR; O'Donnell KA; Wentzel EA; Montgomery CL; Hwang HW; Chang TC; Vivekanandan P; Torbenson M; Clark KR; Mendell JR; Mendell JT. 2009. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137(6):1005-17. [PubMed: 19524505]  [MGI Ref ID J:151413]

May D; Djonov V; Zamir G; Bala M; Safadi R; Sklair-Levy M; Keshet E. 2011. A transgenic model for conditional induction and rescue of portal hypertension reveals a role of VEGF-mediated regulation of sinusoidal fenestrations. PLoS One 6(7):e21478. [PubMed: 21779329]  [MGI Ref ID J:176264]

Ney JT; Schmidt T; Kurts C; Zhou Q; Eckert D; Felsher DW; Schorle H; Knolle P; Tuting T; Barchet W; Buttner R; Limmer A; Gutgemann I. 2009. Autochthonous liver tumors induce systemic T cell tolerance associated with T cell receptor down-modulation. Hepatology 49(2):471-81. [PubMed: 19105207]  [MGI Ref ID J:186226]

O'Donnell KA; Keng VW; York B; Reineke EL; Seo D; Fan D; Silverstein KA; Schrum CT; Xie WR; Mularoni L; Wheelan SJ; Torbenson MS; O'Malley BW; Largaespada DA; Boeke JD. 2012. A Sleeping Beauty mutagenesis screen reveals a tumor suppressor role for Ncoa2/Src-2 in liver cancer. Proc Natl Acad Sci U S A 109(21):E1377-86. [PubMed: 22556267]  [MGI Ref ID J:184782]

Ribeiro AC; Ceccarini G; Dupre C; Friedman JM; Pfaff DW; Mark AL. 2011. Contrasting effects of leptin on food anticipatory and total locomotor activity. PLoS One 6(8):e23364. [PubMed: 21853117]  [MGI Ref ID J:176508]

Roy CN; Mak HH; Akpan I; Losyev G; Zurakowski D; Andrews NC. 2007. Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation. Blood 109(9):4038-44. [PubMed: 17218383]  [MGI Ref ID J:145326]

Saddic LA; Wirt S; Vogel H; Felsher DW; Sage J. 2011. Functional Interactions between Retinoblastoma and c-MYC in a Mouse Model of Hepatocellular Carcinoma. PLoS One 6(5):e19758. [PubMed: 21573126]  [MGI Ref ID J:172430]

Schonig K; Kentner D; Gossen M; Baldinger T; Miao J; Welzel K; Vente A; Bartsch D; Bujard H. 2011. Development of a BAC vector for integration-independent and tight regulation of transgenes in rodents via the Tet system. Transgenic Res 20(3):709-20. [PubMed: 20640885]  [MGI Ref ID J:172622]

Shachaf CM; Kopelman AM; Arvanitis C; Karlsson A; Beer S; Mandl S; Bachmann MH; Borowsky AD; Ruebner B; Cardiff RD; Yang Q; Bishop JM; Contag CH; Felsher DW. 2004. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 431(7012):1112-7. [PubMed: 15475948]  [MGI Ref ID J:93899]

Skvorak KJ; Hager EJ; Arning E; Bottiglieri T; Paul HS; Strom SC; Homanics GE; Sun Q; Jansen EE; Jakobs C; Zinnanti WJ; Gibson KM. 2009. Hepatocyte transplantation (HTx) corrects selected neurometabolic abnormalities in murine intermediate maple syrup urine disease (iMSUD). Biochim Biophys Acta 1792(10):1004-10. [PubMed: 19699299]  [MGI Ref ID J:164850]

Sun Y; Quinn B; Xu YH; Leonova T; Witte DP; Grabowski GA. 2006. Conditional expression of human acid beta-glucosidase improves the visceral phenotype in a Gaucher disease mouse model. J Lipid Res 47(10):2161-70. [PubMed: 16861620]  [MGI Ref ID J:116525]

Tao GZ; Lehwald N; Jang KY; Baek J; Xu B; Omary MB; Sylvester KG. 2013. Wnt/beta-catenin signaling protects mouse liver against oxidative stress-induced apoptosis through the inhibition of forkhead transcription factor FoxO3. J Biol Chem 288(24):17214-24. [PubMed: 23620592]  [MGI Ref ID J:199603]

Tilli MT; Furth PA. 2003. Conditional mouse models demonstrate oncogene-dependent differences in tumor maintenance and recurrence. Breast Cancer Res 5(4):202-5. [PubMed: 12817992]  [MGI Ref ID J:84503]

Tward AD; Jones KD; Yant S; Cheung ST; Fan ST; Chen X; Kay MA; Wang R; Bishop JM. 2007. Distinct pathways of genomic progression to benign and malignant tumors of the liver. Proc Natl Acad Sci U S A 104(37):14771-14776. [PubMed: 17785413]  [MGI Ref ID J:124960]

Wang R; Ferrell LD; Faouzi S; Maher JJ; Bishop JM. 2001. Activation of the met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice. J Cell Biol 153(5):1023-34. [PubMed: 11381087]  [MGI Ref ID J:69731]

Woodard LE; Keravala A; Jung WE; Wapinski OL; Yang Q; Felsher DW; Calos MP. 2010. Impact of hydrodynamic injection and phiC31 integrase on tumor latency in a mouse model of MYC-induced hepatocellular carcinoma. PLoS One 5(6):e11367. [PubMed: 20614008]  [MGI Ref ID J:161998]

Yang YA; Zhang GM; Feigenbaum L; Zhang YE. 2006. Smad3 reduces susceptibility to hepatocarcinoma by sensitizing hepatocytes to apoptosis through downregulation of Bcl-2. Cancer Cell 9(6):445-57. [PubMed: 16766264]  [MGI Ref ID J:110133]

Tg(tetO-DBT)A1Geh related

Skvorak KJ; Hager EJ; Arning E; Bottiglieri T; Paul HS; Strom SC; Homanics GE; Sun Q; Jansen EE; Jakobs C; Zinnanti WJ; Gibson KM. 2009. Hepatocyte transplantation (HTx) corrects selected neurometabolic abnormalities in murine intermediate maple syrup urine disease (iMSUD). Biochim Biophys Acta 1792(10):1004-10. [PubMed: 19699299]  [MGI Ref ID J:164850]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, mice that are heterozygous for the targeted mutation and carriers of both transgenes can be bred together. Loss of one or both of the transgenes results in perinatal lethality (and Maple Syrup Urine Disease or MSUD phenotype) for mice homozygous for the targeted mutation.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


 

This strain is currently On Hold.
Register Interest

To request more information use the Customer Support Contact Form or call 1-800-422-6423 or 1-207-288-5845

View All Strains Awaiting Transfer from the Donor, In Progress and On Hold

Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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phone:207-288-6470

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