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

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Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Strain Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Targeted Mutation Species laboratory 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 Name		R1
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

Madh3^tm1Par

Related Strains

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)

Smad3^tm1Par 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

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Price and Supply Information

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

Price Details

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Supply Details

Standard Supply	Repository-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 Information	View 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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