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Strain Name:

129-Smad3tm1Par/J

Stock Number:

003451

Availability:

Repository-Cryopreserved


General Terms and Conditions

Former Name      129-Madh3tm1Par/J    (Changed: 15-DEC-04 )
      129S2/SvPasIco-Madh3tm1Par/J    (Changed: 15-DEC-04 )
Genes & Alleles   Smad3;   Smad3tm1Par;


Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Strain
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Targeted Mutation
Specieslaboratory mouse
Donating Investigator Luis Parada,   UT Southwestern Medical Center

Strain Description
Mice homozygous for the targeted mutation are viable. Although fertile, they produce litters at reduced efficacy compared to wild type or heterozygous mice. Null mutants are approximately 20%-30% smaller than heterozygous or wildtype litter mates, with males exhibiting a more pronounced size reduction. Reporter lacZ expression is observed in many developing embryonic tissues with highest levels in mesenchymal derivatives. Expression in adult mutant mice is observed in the colon, with highest levels in the muscularis propria and submucosa with lower levels in the epithelium. At approximately 4-6 months of age, they develop gastric tumors. The donating investigator originally described spontaneous, deeply invasive colorectal adenocarcinomas that penetrate through all layers of the intestinal wall and metastasize to lymph nodes. Colorectal adenocarcinomas are not a component of the phenotype observed in this strain at The Jackson Laboratory. However, the gastric epithelium was found to contain neoplasms that were of a mixed nature. This deviation from the original phenotype may possibly be attributed to differing environmental conditions existing at The Jackson Laboratory facilities and those at the originating institution.

Strain Development
This targeted mutation was made in the laboratory of Dr. Luis F. Parada at The University of Texas Southwestern Medical Center. The targeting vector includes a neo cassette and was designed to disrupt the second exon of the locus. In addition, a lacZ gene and an internal ribosomal entry site (IRES) were introduced to permit translation of the beta galactosidase reporter from the interrupted transcript. The IRES-lacZ-neo inserted in the second exon truncates the gene and creates loss-of-function gene product proteins. Alternative splicing around exon 2 shifts the open reading frame. The 129X1/SvJ x 129S1/Sv-dervied R1 ES cell line was used. Chimeric mice carrying the targeted mutation were backcrossed to the 129S2/SvPasIco strain.

Mammalian Phenotype Terms assigned by genotype

Smad3tm1Par/Smad3tm1Par

        either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:49839)
    • decreased life span; more pronounced in the 129/Sv background than in the mixed 129/Sv and C57BL/6 background, but evident in both
  • tumorigenesis
  • altered tumor susceptibility/resistance (MGI Ref ID J:49839)
    • increased metastatic potential (MGI Ref ID J:49839)
      • evidence of metastasis to lymph nodes is seen on the 129/Sv background
    • intestinal adenocarcinoma (MGI Ref ID J:49839)
      • penetrance of adenocarcinoma is about 30% on the mixed 129/Sv and C57BL/6 background and 100% on the 129/Sv background
      • mutants on the mixed background show greater variability in the time course of tumors and tumors are less aggressive and smaller than in the 129/Sv background
      • a wide range of tumors are found within a single mouse, including lesions that appear to be polyps
  • growth/size phenotype
  • decreased body size (MGI Ref ID J:49839)
    • about 20% - 30% smaller than controls
    • males exhibit a greater size reduction than females
  • distended abdomen (MGI Ref ID J:49839)
    • due to tumors
  • reproductive system phenotype
  • abnormal fertility/fecundity (MGI Ref ID J:49839)
    • mice are fertile, but have reduced efficacy in producing litters
  • behavior/neurological phenotype
  • abnormal posture (MGI Ref ID J:49839)
    • abnormal, rounded posture, but no associated skeletal defects
  • lethargy (MGI Ref ID J:49839)
    • as mutants age beyond 18 weeks, they exhibit signs of distress that include lethargy
  • digestive/alimentary phenotype
  • intestinal obstruction (MGI Ref ID J:49839)
    • due to tumors
  • rectal prolapse (MGI Ref ID J:49839)
    • due to tumors; more pronounced on the 129/Sv background than on the mixed 129/Sv and C57BL/6 background, with 75% of mutants showing prolapse by 24 weeks of age
  • skin/coat/nails phenotype
  • ruffled hair (MGI Ref ID J:49839)
    • as mutants age beyond 18 weeks, they exhibit signs of distress that include fur-ruffling

Smad3tm1Par/Smad3tm1Par

        129-Smad3tm1Par/J
  • tumorigenesis
  • intestinal adenocarcinoma (MGI Ref ID J:106572)
    • mutants maintained free of the gram-negative enterohepatic bacteria Helicobacter for up to 9 months do not develop colon cancer as do mutants housed under normal conditions
    • infection of mutants with Helicobacter triggers colon cancer in 50-66% of mutants; mucinous adenocarcinomas develop 5 to 30 weeks after infection
  • immune system phenotype
  • increased inflammatory response (MGI Ref ID J:106572)
    • colonic tissue of uninfected mutants is in a proinflammatory state as indicated by increased mRNA levels of IL-6, TNF-alpha, IFN-gamma, and IL-4, which is exacerbated by Helicobacter infection

Gene & Allele Details

Allele Symbol Smad3tm1Par
Allele Name targeted mutation 1, Luis F Parada
Common Name(s) Madh3-; Smad3-; Smad3tm1par-;
Mutation Made By Luis Parada,   UT Southwestern Medical Center
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<+>
Gene Symbol and Name Smad3, MAD homolog 3 (Drosophila)
Chromosome 9
Gene Common Name(s) AU022421; DKFZP586N0721; DKFZp686J10186; HSPC193; HsT17436; JV15-2; MADH3; MGC60396; Madh3; Smad 3; expressed sequence AU022421;
Molecular Note An IRES-LacZ-neo cassette was inserted into exon 2 of the gene, truncating the carboxyl-terminal active domain of the protein. In addition, this cassette was inserted in a region where point mutations create loss-of-function proteins. Finally, alternative splicing around the disrupted exon would shift the open reading frame. [MGI Ref ID J:49839]

Control Information

  Allele   Control
 Smad3tm1Par  Wild-type from the colony
 
  Considerations for Choosing Controls

Genotyping Protocols

Madh3tm1Par

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lacZ Expression Strains
002484   129-Alpltm1Sor/J
002292   129-Gt(ROSA)26Sor/J
006050   129-Sirt6tm1Fwa/J
003310   129S-Gt(ROSA)26Sortm1Sor/J
003383   129S-Nogtm1Amc/J
004545   129S-Npytm1Rpa/J
005091   129S-Pnpla6tm1Blw/J
007199   129S-Sgpl1Gt(ROSA)78Sor/J
003082   129S1/SvImJ-Bcl2tm1Mpin/J
004478   B6.129-Foxd1tm1Lai/J
006939   B6.129-Fut1tm1Sdo/J
005768   B6.129-Htr5atm1Dgen/J
002938   B6.129-Kdrtm1Jrt/J
004158   B6.129-Maftm1Gsb/J
006497   B6.129-Skiltm2Spw/J
005772   B6.129P2-Acvrl1tm1Dgen/J
006431   B6.129P2-Adam21tm1Dgen/J
005770   B6.129P2-Adamts4tm1Dgen/J
005771   B6.129P2-Adamts5tm1Dgen/J
005773   B6.129P2-Adcy3tm1Dgen/J
005774   B6.129P2-Adcy7tm1Dgen/J
005775   B6.129P2-Adipor2tm1Dgen/J
005776   B6.129P2-Avpr1atm1Dgen/J
005777   B6.129P2-Axltm1Dgen/J
005783   B6.129P2-Cacna1ctm1Dgen/J
005780   B6.129P2-Cacna2d3tm1Dgen/J
005781   B6.129P2-Cacng3tm1Dgen/J
005782   B6.129P2-Cacng4tm1Dgen/J
005784   B6.129P2-Capn5tm1Dgen/J
005785   B6.129P2-Capn7tm1Dgen/J
005792   B6.129P2-Ccr1l1tm1Dgen/J
005793   B6.129P2-Ccr6tm1Dgen/J
005794   B6.129P2-Ccr7tm1Dgen/J
005779   B6.129P2-Celsr2tm1Dgen/J
005797   B6.129P2-Chrna2tm1Dgen/J
005787   B6.129P2-Ctsctm1Dgen/J
005796   B6.129P2-Cxcr3tm1Dgen/J
005798   B6.129P2-Drd5tm1Dgen/J
005800   B6.129P2-Efemp2tm1Dgen/J
005801   B6.129P2-Esrratm1Dgen/J
005802   B6.129P2-Faim2tm1Dgen/J
006262   B6.129P2-Fut2tm1Sdo/J
005803   B6.129P2-Fzd1tm1Dgen/J
005804   B6.129P2-Fzd8tm1Dgen/J
005811   B6.129P2-Gabra3tm1Dgen/J
005812   B6.129P2-Gabra4tm1Dgen/J
005810   B6.129P2-Gabrptm1Dgen/J
005809   B6.129P2-Galr1tm1Dgen/J
005816   B6.129P2-Glra3tm1Dgen/J
005805   B6.129P2-Gpr151tm1Dgen/J
005806   B6.129P2-Gpr37tm1Dgen/J
005807   B6.129P2-Gpr6tm1Dgen/J
005813   B6.129P2-Grik5tm1Dgen/J
005808   B6.129P2-Grk5tm1Dgen/J
005814   B6.129P2-Grm1tm1Dgen/J
005815   B6.129P2-Grm3tm1Dgen/J
005817   B6.129P2-Gsk3btm1Dgen/J
005818   B6.129P2-Hcrtr1tm1Dgen/J
005767   B6.129P2-Htr4tm1Dgen/J
005769   B6.129P2-Htr7tm1Dgen/J
005830   B6.129P2-Kcnq2tm1Dgen/J
005821   B6.129P2-Lats2tm1Dgen/J
005822   B6.129P2-Lmbr1tm1Dgen/J
005850   B6.129P2-Mapkapk2tm1Dgen/J
005824   B6.129P2-Mmp17tm1Dgen/J
005825   B6.129P2-Mtmr1tm1Dgen/J
005778   B6.129P2-Naip1tm1Dgen/J
005826   B6.129P2-Ntsr1tm1Dgen/J
005829   B6.129P2-Pkd2l2tm1Dgen/J
005828   B6.129P2-Ppardtm1Dgen/J
005831   B6.129P2-Ppm1ftm1Dgen/J
005827   B6.129P2-Ptch2tm1Dgen/J
005832   B6.129P2-Ptprotm1Dgen/J
005799   B6.129P2-S1pr4tm1Dgen/J
005837   B6.129P2-Scn11atm1Dgen/J
005836   B6.129P2-Scn9atm1Dgen/J
005834   B6.129P2-Sema5atm1Dgen/J
005835   B6.129P2-Sema6ctm1Dgen/J
006432   B6.129P2-Slc18a1tm1Dgen/J
005839   B6.129P2-Slc22a12tm1Dgen/J
005838   B6.129P2-Slc22a6tm1Dgen/J
005840   B6.129P2-Slc40a1tm1Dgen/J
005841   B6.129P2-Slc6a9tm1Dgen/J
005842   B6.129P2-Slc7a8tm1Dgen/J
005843   B6.129P2-Slc9a6tm1Dgen/J
005844   B6.129P2-Sstr1tm1Dgen/J
005847   B6.129P2-Tgfbr1tm1Dgen/J
005845   B6.129P2-Thbs4tm1Dgen/J
005790   B6.129P2-Tpp1tm1Dgen/J
005848   B6.129P2-Trpm5tm1Dgen/J
005791   B6.129P2-Xcr1tm1Dgen/J
003474   B6.129S4-Gt(ROSA)26Sortm1Sor/J
005901   B6.129S4-Ppardtm2Rev/J
006142   B6.129S4-Ppargtm1Rev/J
003754   B6.129S4-Shroom3Gt(ROSA)53Sor/J
005119   B6.129S6-Npas2tm1Slm/J
002741   B6.129S7-Alpltm1Sor/J
005970   B6.129S7-Atoh1tm2Hzo/J
006039   B6.129S7-Efnb2tm1And/J
002192   B6.129S7-Gt(ROSA)26Sor/J
005981   B6.129S7-Rai1tm1Jrl/J
005039   B6.129X1-Adra1atm1Pcs/J
005085   B6.Cg-Cd44tm1Hbg/J
007745   B6.Cg-Mirn155tm1.1Rsky/J
005317   B6.Cg-Tg(BAT-lacZ)3Picc/J
006055   B6.Cg-Tg(CAG-Bgeo,-DsRed*MST)1Nagy/J
004178   B6.Cg-Tg(CAG-Bgeo/GFP)21Lbe/J
006477   B6.Cg-Tg(CAG-lacZ-WGA)330Bbm/J
003139   B6.Cg-Tg(DBHn-lacZ)8Rpk/J
006229   B6.Cg-Tg(DRE-lacZ)2Gswz/J
002982   B6.Cg-Tg(xstpx-lacZ)32And/J
003504   B6;129-Gt(ROSA)26Sortm1Sho/J
005064   B6;129-Slc30a3tm1Rpa/J
005788   B6;129P2-Cd97tm1Dgen/J
005833   B6;129P2-Rgs4tm1Dgen/J
002073   B6;129S-Gt(ROSA)26Sor/J
006470   B6;129S-Hopxtm1Eno/J
004153   B6;129S-Mtap7Gt(ROSABetageo)1Sor/J
006958   B6;129S-Nkd1tm1Kwha/J
006960   B6;129S-Nkd2tm1Kwha/J
007204   B6;129S4-2610005L07RikGt(ROSA)73Sor/J
003309   B6;129S4-Gt(ROSA)26Sortm1Sor/J
004365   B6;129S6-Srebf1tm1Mbr/J
002317   B6;129S7-Alpltm1Sor/J
003266   B6;129S7-Epas1tm1Rus/J
006044   B6;129S7-Ephb4tm1And/J
003471   B6;C3H-Tg(CNP-GEO)1Ldh/J
006465   B6;CBA-Tg(CAG-lacZ-WGA)330Bbm/J
006680   B6;CBA-Tg(Olfr16*,taulacZ)19Mom/MomJ
006671   B6;CBA-Tg(Olfr16*,taulacZ)5Mom/MomJ
006672   B6;CBA-Tg(Olfr16*,taulacZ)7Mom/MomJ
006673   B6;CBA-Tg(Olfr16,taulacZ)sn2Mom/MomJ
004141   B6;CBA-Tg(UAS-lacZ)65Rth/J
002369   B6;SJL-Tg(c177-lacZ)226Bri/J
002372   B6;SJL-Tg(c177-lacZ)227Bri/J
002621   B6;SJL-Tg(tetop-lacZ)2Mam/J
003299   B6;SWJ-Tg(TIMP3-lacZ)7Jeb/J
002865   B6CBA-Tg(Wnt1-lacZ)206Amc/J
002955   C.129S7-Gt(ROSA)26Sor/J
002754   C57BL/6-Tg(LacZpl)60Vij/J
002193   C57BL/6J-Tg(MTn-lacZ)204Bri/J
002981   DBA/2-Tg(xstpx-lacZ)36And/J
004127   FVB-Tg(Nes-rtTA)306Rvs/J
007225   FVB.129(B6)-Usp18tm1Dzh/J
008203   FVB.Cg-Smn1tm1Msd Tg(ACTA1-SMN)63Ahmb Tg(SMN2)89Ahmb/J
008209   FVB.Cg-Smn1tm1Msd Tg(ACTA1-SMN)69Ahmb Tg(SMN2)89Ahmb/J
006214   FVB.Cg-Smn1tm1Msd/J
005024   FVB.Cg-Tg(SMN2)89Ahmb Smn1tm1Msd/J
005026   FVB.Cg-Tg(SMN2)89Ahmb Tg(SMN1*A2G)2023Ahmb Smn1tm1Msd/J
005025   FVB.Cg-Tg(SMN2*delta7)4299Ahmb Tg(SMN2)89Ahmb Smn1tm1Msd/J
003140   FVB/N-Tg(PAI1-lacZ)1Jjb/J
002856   FVB/N-Tg(TIE2-lacZ)182Sato/J
005941   FVB/N-Tg(tetO-Aurkb,lacZ)41Kra/J
003315   FVB/N-Tg(tetORo1-lacZ)3Conk/J
003487   FVB/NJ-Tg(XGFAP-lacZ)3Mes/J
005878   NOD.Cg-Cd44tm1Hbg/J
003899   STOCK Cd44tm1Hbg/J
006241   STOCK Hhiptm1Amc/J
006578   STOCK Myoz2tm1Eno/J
005707   STOCK Rag1tm1Mom Tg(TIE2-lacZ)182Sato/J
008212   STOCK Smn1tm1Msd Tg(Prnp-SMN)92Ahmb Tg(SMN2)89Ahmb/J
006882   STOCK Tg(CAG-Bgeo,-AML1/ETO,-ALPP)1Lbe/J
005438   STOCK Tg(CAG-Bgeo,-DsRed*MST)1Nagy/J
006850   STOCK Tg(CAG-Bgeo,-NOTCH1,-EGFP)1Lbe/J
006876   STOCK Tg(CAG-Bgeo,-TEL/AML1,-EGFP)A6Lbe/J
006613   STOCK Tg(CAG-Bgeo,-Tle1,-ALPP)1Lbe/J
003919   STOCK Tg(CAG-Bgeo/ALPP)1Lbe/J
003920   STOCK Tg(CAG-Bgeo/GFP)21Lbe/J
004623   STOCK Tg(Fos-lacZ)34Efu/J
006674   STOCK Tg(Olfr16,taulacZ)2030Mom/MomJ
005493   STOCK Tg(Tek-rtTA,TRE-lacZ)1425Tpr/J
002395   STOCK Tg(Zfy1-lacZ)218Bri/J
003274   STOCK Tg(tetNZL)2Bjd/J
005728   STOCK Tg(tetO-Ipf1,lacZ)958.1Macd/J
View lacZ Expression Strains     (174 strains)

Additional Web Information

Fluorescent Proteins/lacZ Systems
Genetic Quality Control Annual Report
New 129 Nomenclature Bulletin

Research Applications

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

Cancer Research
Increased Tumor Incidence (Adenomas: intestinal adenomas)
Increased Tumor Incidence (Other Tissues/Organs: colorectal adenocarcinoma, metastases found in other organs)

Internal/Organ Research
Gastrointestinal Defects

Reproductive Biology Research
Fertility Defects

Research Tools
lacZ Expression
Cancer Research (tumor immunology)

Smad3tm1Par related

Cancer Research
Increased Tumor Incidence (Other Tissues/Organs: colorectal adenocarcinoma, metastases found in other organs)

References

Selected Reference(s)

Zhu Y; Richardson JA; Parada LF; Graff JM. 1998. Smad3 mutant mice develop metastatic colorectal cancer. Cell 94(6):703-14. [PubMed: 9753318]  [MGI Ref ID J:49839]

Additional References

Price and Supply Information

Strain Name: 129-Smad3tm1Par/J
Stock Number: 003451

Price Details

IMPORTANT NOTE: Prices are based on shipping destination. To view prices, select your shipping destination.

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to the Supply Notes for further information.
Supply Notes Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.

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Control InformationView Control Information in Strain Details.

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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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