Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   05-JUN-12 Species laboratory mouse Generation N9+F3 (14-FEB-13) Generation Definitions   Donating Investigator Xin-Yuan Fu,   Indiana University School of Medicine

Description
These mice possess loxP sites on either side of exons 18, 19 and 20 of the targeted gene. Exons 19 and 20 encode the SH2 domain. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 18, 19 and 20 deleted in the cre-expressing tissues.

When bred to a strain with Cre recombinase expression in the liver, under the control of the Ttr, transthyretin, promoter, this mutant mouse strain may be useful in studies of liver regeneration.

When bred to a strain with Cre recombinase expression in cardiac tissue (see Stock No. 011037 for example) , this mutant mouse strain may be useful in studies of inflammation-induced cardiac injury.

When bred to a strain with Cre recombinase expression in the bone marrow and endothelial cells, under the control of the Tek (Tie2), endothelial-specific receptor tyrosine kinase, promoter, the resulting mice develop a Crohn's disease-like phenotype.

Development
A loxP site flanked targeting vector containing a floxed NEO cassette was utilized in the construction of this mutant. This selection cassette was inserted upstream of exon 18 of the targeted gene, and another loxP site was inserted downstream of exon 20. This construct was electroporated into 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺ derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to transgenic Ttr10-1 deleter mice, on the C57BL/6 genetic background, which express Cre recombinase in almost all tissues including germline cells. Mice that retained the loxP site flanked exons 18, 19 and 20, and no longer carried the NEO cassette were then bred to C57BL/6 mice to remove the cre transgene. The mice were then backcrossed to C57BL/6 for 9 to 12 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Stat3

008862

129X1-Stat3tm1Desi/J

View Strains carrying other alleles of Stat3     (1 strain)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Hyper-Ige Recurrent Infection Syndrome, Autosomal Dominant   (STAT3)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Stat3^tm1Xyfu/Stat3⁺

        involves: 129S1/Sv * C57BL/6

• mortality/aging
• increased sensitivity to induced morbidity/mortality
  • mortality during the first 12 hours following 70% hepatectomy is 5.5%   (MGI Ref ID J:128719)

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Stat3^tm1Xyfu/Stat3⁺ Tg(Myh6-cre)2182Mds/0

        involves: 129S1/Sv * FVB/N   (conditional)

• immune system phenotype
• increased susceptibility to endotoxin shock
  • LPS-treated mice exhibit increased TNF-alpha levels in cardiac myocytes compared with similarly treated wild-type mice although not as severely as in homozygous mice   (MGI Ref ID J:86400)
• increased tumor necrosis factor secretion
  • in the cardiac myocytes of LPS-treated mice   (MGI Ref ID J:86400)
• cardiovascular system phenotype
• cardiac fibrosis
  • severe at 9 months   (MGI Ref ID J:86400)

View Research Applications

Research Applications

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

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Stat3tm1Xyfu
Allele Name		targeted mutation 1, Xin-Yuan Fu
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Stat3flox;
Mutation Made By		Xin-Yuan Fu,   Indiana University School of Medicine
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name		Stat3, signal transducer and activator of transcription 3
Chromosome		11
Gene Common Name(s)		1110034C02Rik; APRF; AW109958; HIES; RIKEN cDNA 1110034C02 gene; expressed sequence AW109958;
Molecular Note		A floxed neo cassette was inserted into intron 17 and an additional loxP site was inserted into intron 20. The neo cassette was removed by cre-mediated recombination to leave exons 18, 19 and 20 flanked by loxP sites. [MGI Ref ID J:128719] [MGI Ref ID J:86400]

Genotyping

Genotyping Information

Genotyping Protocols

Stat3^tm1Xyfu alternative1, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Moh A; Iwamoto Y; Chai GX; Zhang SS; Kano A; Yang DD; Zhang W; Wang J; Jacoby JJ; Gao B; Flavell RA; Fu XY. 2007. Role of STAT3 in liver regeneration: survival, DNA synthesis, inflammatory reaction and liver mass recovery. Lab Invest 87(10):1018-28. [PubMed: 17660847]  [MGI Ref ID J:128719]

Additional References

Stat3^tm1Xyfu related

Cai Z; Simons DL; Fu XY; Feng GS; Wu SM; Zhang X. 2011. Loss of shp2-mediated mitogen-activated protein kinase signaling in muller glial cells results in retinal degeneration. Mol Cell Biol 31(14):2973-83. [PubMed: 21576358]  [MGI Ref ID J:174095]

Goodman MD; Koch SE; Afzal MR; Butler KL. 2010. STAT SUBTYPE SPECIFICITY AND ISCHEMIC PRECONDITIONING IN MICE: IS STAT-3 ENOUGH? Am J Physiol Heart Circ Physiol :. [PubMed: 21131482]  [MGI Ref ID J:167215]

Jacoby JJ; Kalinowski A; Liu MG; Zhang SS; Gao Q; Chai GX; Ji L; Iwamoto Y; Li E; Schneider M; Russell KS; Fu XY. 2003. Cardiomyocyte-restricted knockout of STAT3 results in higher sensitivity to inflammation, cardiac fibrosis, and heart failure with advanced age. Proc Natl Acad Sci U S A 100(22):12929-34. [PubMed: 14566054]  [MGI Ref ID J:86400]

Moh A; Zhang W; Yu S; Wang J; Xu X; Li J; Fu XY. 2008. STAT3 sensitizes insulin signaling by negatively regulating glycogen synthase kinase-3 beta. Diabetes 57(5):1227-35. [PubMed: 18268048]  [MGI Ref ID J:135248]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   05-JUN-12
Diet Information	LabDiet® 5K20

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
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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