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 STOCK Cd44tm1Ugu/J    (Changed: 05-DEC-08 ) SJL.129-Cd44tm1Ugu/J    (Changed: 06-JUN-08 ) Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N10+F4p Generation Definitions   Donating Investigator Ursula Gunthert,   University of Basel

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. These mice possess loxP sites on either side of exon 6 of the targeted gene. RT-PCR analysis reveals that exon 7 is not expressed in the floxed mice, and Southern blots confirm that 1.6kb of exon 7 was deleted during homologous recombination. When these mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have exon 6 and exon 7 deleted in the cre-expressing tissue(s). According to the donating investigator, homozygotes exhibit reduced incidence and severity of induced experimental autoimmune encephalomyelitis (EAE) when compared to wildtype controls. This mutant mouse strain may be useful in studies of multiple sclerosis (MS) and inflammatory diseases.

NOTE: Stock No. 008008 mice are on a unique "SJL/R" genetic background; the "SJL/R" strain was maintained by the Erasmus Medical Center (Rotterdam, The Netherlands) as a unique substrain of SJL that showed more favorable responses to EAE induction.

NOTE: On a 129/Sv genetic background, homozygotes are resistant to trinitrobenzene sulfonic acid (TNBS)-induced colitis.

Development
A targeting vector containing a loxP site-flanked neomycin resistance cassette inserted upstream and a third loxP site inserted downstream of exon 6 of the targeted gene was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Approximately 1.6kb of exon 7 also was deleted from the targeted gene during homologous recombination. The resulting chimeric mice were bred to "SJL/R" mice (from Erasmus Medical Center, Rotterdam, The Netherlands) for 10 generations prior to arrival at The Jackson Laboratory. Upon arrival, female and male mutant mice were bred together to preserve the unique genetic background of this strain.

NOTE: The "SJL/R" strain was maintained by the Erasmus Medical Center (Rotterdam, The Netherlands) as a unique substrain of SJL that showed more favorable responses to EAE induction. A 27 SNP (single nucleotide polymorphism) panel analysis performed on the Cd44-mutant mice that were rederived by The Jackson Laboratory revealed 4 loci that were homozygous for markers other than SJL/J. These loci are on chromosome 3 (approximately 16.3 cM), chromosome 9 (approximately 6.6 cM), chromosome 11 (approximately 9.8 cM), and chromosome 18 (approximately 26.2 cM). The Jackson Laboratory obtained "SJL/R" splenocyte DNA from the Erasmus Medical Center and report an identical SNP profile using the same 27 SNP panel analysis.

Control Information

	Control
	000686 SJL/J	(approximate) NOTE: Stock No. 008008 mice are on a unique "SJL/R" genetic background; the "SJL/R" strain was maintained by the Erasmus Medical Center (Rotterdam, The Netherlands) as a unique substrain of SJL that showed more favorable responses to EAE induction.
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Cd44

005085	B6.129(Cg)-Cd44tm1Hbg/J
012239	B6.129(Cg)-Cd44tm1Hbg/SjJ
005878	NOD.129(Cg)-Cd44tm1Hbg/J
003899	STOCK Cd44tm1Hbg/J

View Strains carrying other alleles of Cd44     (4 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

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.

Cd44^tm1Ugu/Cd44^tm1Ugu

        involves: 129/Sv * C57BL/6

• digestive/alimentary phenotype
• abnormal digestive system physiology
  • 3-4X increase of apoptotic cells in colons after injury but not without injury   (MGI Ref ID J:62867)
• immune system phenotype
• *normal* immune system phenotype
  • 81% as opposed to 44% of mice survived acute colon injury and did not develop colitis   (MGI Ref ID J:62867)
• • abnormal T-helper 1 physiology
    • Th1-type cytokines down regulated   (MGI Ref ID J:62867)
  • abnormal T-helper 2 physiology
    • Th2-type cytokines up regulated   (MGI Ref ID J:62867)

View Research Applications

Research Applications

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

Immunology and Inflammation Research
Autoimmunity
      experimental allergic encephalomyelitis (EAE)

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Cd44tm1Ugu
Allele Name		targeted mutation 1, Ursula Gunthert
Allele Type		Targeted (knock-out)
Common Name(s)		CD44v7-;
Mutation Made By		Ursula Gunthert,   University of Basel
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		Cd44, CD44 antigen
Chromosome		2
Gene Common Name(s)		AU023126; AW121933; AW146109; CD44A; CDW44; CSPG8; ECMR-III; HCELL; HERMES; HUTCH-I; IN; LHR; Ly-24; MC56; MDU2; MDU3; METAA; MIC4; Pgp-1; Pgp1; RHAMM; expressed sequence AU023126; expressed sequence AW121933; expressed sequence AW146109; lymphocyte antigen 24; phagocyte glycoprotein 1;
Molecular Note		A loxP site was inserted 3' of exon v6 while a neomycin resistance cassette with a 5' loxP site was inserted 5' of exon v6. During insertion, 1.6 kb of sequence was lost in the exon v7 region leading to deficient expression of this variant in homozygous mutant mice. [MGI Ref ID J:62867]

Genotyping

Genotyping Information

Genotyping Protocols

Cd44^tm1Ugu, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Wittig BM; Johansson B; Zoller M; Schwarzler C; Gunthert U. 2000. Abrogation of experimental colitis correlates with increased apoptosis in mice deficient for CD44 variant exon 7 (CD44v7). J Exp Med 191(12):2053-64. [PubMed: 10859330]  [MGI Ref ID J:62867]

Additional References

Cd44^tm1Ugu related

Abel B; Kurrer M; Shamshiev A; Marty RR; Eriksson U; Gunthert U; Kopf M. 2006. The osteopontin - CD44 pathway is superfluous for the development of autoimmune myocarditis. Eur J Immunol 36(2):494-9. [PubMed: 16402410]  [MGI Ref ID J:113855]

Christ O; Gunthert U; Haas R; Zoller M. 2001. Importance of CD44v7 isoforms for homing and seeding of hematopoietic progenitor cells. J Leukoc Biol 69(3):343-52. [PubMed: 11261780]  [MGI Ref ID J:68127]

Hoffmann U; Heilmann K; Hayford C; Stallmach A; Wahnschaffe U; Zeitz M; Gunthert U; Wittig BM. 2007. CD44v7 ligation downregulates the inflammatory immune response in Crohn's disease patients by apoptosis induction in mononuclear cells from the lamina propria. Cell Death Differ 14(8):1542-51. [PubMed: 17479111]  [MGI Ref ID J:139267]

Marhaba R; Bourouba M; Zoller M. 2003. CD44v7 interferes with activation-induced cell death by up-regulation of anti-apoptotic gene expression. J Leukoc Biol 74(1):135-48. [PubMed: 12832452]  [MGI Ref ID J:133078]

McKallip RJ; Fisher M; Do Y; Szakal AK; Gunthert U; Nagarkatti PS; Nagarkatti M. 2003. Targeted deletion of CD44v7 exon leads to decreased endothelial cell injury but not tumor cell killing mediated by interleukin-2-activated cytolytic lymphocytes. J Biol Chem 278(44):43818-30. [PubMed: 12904302]  [MGI Ref ID J:86375]

McKallip RJ; Fisher M; Gunthert U; Szakal AK; Nagarkatti PS; Nagarkatti M. 2005. Role of CD44 and its v7 isoform in staphylococcal enterotoxin B-induced toxic shock: CD44 deficiency on hepatic mononuclear cells leads to reduced activation-induced apoptosis that results in increased liver damage. Infect Immun 73(1):50-61. [PubMed: 15618140]  [MGI Ref ID J:94793]

Rajasagi M; Vitacolonna M; Benjak B; Marhaba R; Zoller M. 2009. CD44 promotes progenitor homing into the thymus and T cell maturation. J Leukoc Biol 85(2):251-61. [PubMed: 18955544]  [MGI Ref ID J:145195]

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, RG10/RG30.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes. NOTE: Stock No. 008008 mice are on a unique "SJL/R" genetic background; the "SJL/R" strain was maintained by the Erasmus Medical Center (Rotterdam, The Netherlands) as a unique substrain of SJL that showed more favorable responses to EAE induction.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000686 SJL/J	(approximate) NOTE: Stock No. 008008 mice are on a unique "SJL/R" genetic background; the "SJL/R" strain was maintained by the Erasmus Medical Center (Rotterdam, The Netherlands) as a unique substrain of SJL that showed more favorable responses to EAE induction.
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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