Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names 129-Tff3tm1Dkpy/J    (Changed: 29-JUL-09 ) Type Mutant Stock; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N1pN1 Generation Definitions   Donating Investigator Daniel K Podolsky,   Massachusetts General Hospital

Description
Mice homozygous for this intestinal trefoil factor (ITF or Tff3) mutant allele are viable and fertile with no RNA or protein expression of the targeted gene in the gastrointestinal tract. Homozygous mice exhibit impaired physiological migration of intestinal epithelium to the mucosal surface, have impaired mucosal healing and increased susceptibility to dextran sulfate sodium (DSS)- induced colitis, and are more susceptible to chemotherapy and radiation-induced mucositis. These intestinal trefoil factor (ITF or Tff3) mutant mice may be useful in studying gastrointestinal tract injury (including inflammatory bowel diseases), maintenance of the mucosal barrier, migration and turnover of the intestinal epithelium, and therapies for colon cancer.

Development
A targeting vector was designed to replace exon 2 of the targeted gene with a neomycin resistance gene cassette. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and chimeric mice were identified. These mutant mice were maintained on a "129" genetic background prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred with 129S1/SvImJ mice for at least one generation to establish the colony.

A 27 SNP (single nucleotide polymorphism) panel analysis performed by The Jackson Laboratory on the rederived mice revealed six segregating markers (each on a different chromosome). All six loci suggest this strain is on a mixed 129;C57BL/6 genetic background (July 2009).

Control Information

	Control
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Tff3^tm1Dkpy/Tff3^tm1Dkpy

        involves: 129S4/SvJae

• digestive/alimentary phenotype
• abnormal intestinal epithelium morphology
  • impaired physiological migration of epithelium to mucosal surface   (MGI Ref ID J:35882)
• increased susceptibility to induced colitis
  • increased development of colitis (colon ulceration, abscesses, and hemorrhage) after dextran sulfate sodium (DSS) administration   (MGI Ref ID J:35882)
• immune system phenotype
• increased susceptibility to induced colitis
  • increased development of colitis (colon ulceration, abscesses, and hemorrhage) after dextran sulfate sodium (DSS) administration   (MGI Ref ID J:35882)
• homeostasis/metabolism phenotype
• increased susceptibility to injury
  • increased development of colitis (colon ulceration, abscesses, and hemorrhage) after dextran sulfate sodium (DSS) administration   (MGI Ref ID J:35882)
  • increased development of bloody diarrhea and death after (DSS) administration   (MGI Ref ID J:35882)
  • increased weight loss after (DSS) administration   (MGI Ref ID J:35882)

View Research Applications

Research Applications

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

Endocrine Deficiency Research
Gastrointestinal Defects

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      Inflammatory bowel disease
Inflammation
      Inflammatory bowel disease

Internal/Organ Research
Gastrointestinal Defects
      colitis
Wound Healing
      delayed/impaired

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tff3tm1Dkpy
Allele Name		targeted mutation 1, Daniel K Podolsky
Allele Type		Targeted (knock-out)
Common Name(s)		Itf-;
Mutation Made By		Daniel Podolsky,   Massachusetts General Hospital
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Tff3, trefoil factor 3, intestinal
Chromosome		17
Gene Common Name(s)		ITF; P1B; TFI; mITF;
Molecular Note		Exon 2 of this gene was replaced with a neo cassette via homologous recombination resulting in the deletion of the trefoil domain. Absence of gene expression in the gastrointestinal tract of homozygous mutant animals was confirmed by Northern blot analysis and immunohistochemistry. [MGI Ref ID J:35882]

Genotyping

Genotyping Information

Genotyping Protocols

Tff3^tm1Dkpy, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Mashimo H; Wu DC; Podolsky DK; Fishman MC. 1996. Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor [see comments] Science 274(5285):262-5. [PubMed: 8824194]  [MGI Ref ID J:35882]

Additional References

Tff3^tm1Dkpy related

Beck PL; Ihara E; Hirota SA; MacDonald JA; Meng D; Nanthakumar NN; Podolsky DK; Xavier RJ. 2010. Exploring the interplay of barrier function and leukocyte recruitment in intestinal inflammation by targeting fucosyltransferase VII and trefoil factor 3. Am J Physiol Gastrointest Liver Physiol 299(1):G43-53. [PubMed: 20299601]  [MGI Ref ID J:162267]

Beck PL; Wong JF; Li Y; Swaminathan S; Xavier RJ; Devaney KL; Podolsky DK. 2004. Chemotherapy- and radiotherapy-induced intestinal damage is regulated by intestinal trefoil factor. Gastroenterology 126(3):796-808. [PubMed: 14988834]  [MGI Ref ID J:107673]

Paulsen FP; Woon CW; Varoga D; Jansen A; Garreis F; Jager K; Amm M; Podolsky DK; Steven P; Barker NP; Sel S. 2008. Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds. J Biol Chem 283(19):13418-27. [PubMed: 18326859]  [MGI Ref ID J:137338]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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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