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

Type Coisogenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Motomu Shimaoka,   Immune Disease Institute (formerly CBRI)

Description
Mice homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Lymphocytes exhibit increased basal adhesiveness to VCAM1 and MAdCAM1 under physiological conditions as well as reduced transmigration across VCAM1 and MAdCAM1 substrates and endothelial monolayers under shear stress. Homing of mutant lymphocytes to the gut is reduced by approximately 50%. In addition, fewer lymphocytes are found in the gut and Peyer's Patches are smaller in size than wild-type. This mutant mouse strain may be useful in studies of leukocyte migration and homing.

Development
A targeting vector was designed to contain exons 26 and 27, an engineered Xba1 site, an ACN cassette, and exon 28, respectively. Exon 28 contains nucleotide mutations to generate an amino acid substitution of alanine for arginine. The loxP-flanked ACN cassette contains the neomycin resistance gene and Cre recombinase gene under the control of the sperm-specific angiotensin-converting enzyme promoter. Cre-mediated recombination during spermatogenesis of chimeric males removes the cassette leaving a single loxP- site between exons 27 and 28. The construct was electroporated into C57BL/6-derived Bruce-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into BALB/c blastocysts, and the resulting chimeric males were crossed to C57BL/6 females. Homozygotes were generated and then maintained by intercross prior to arrival at The Jackson Laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Itga4

002463

B6.129S-Itga4tm1Hyn/J

View Strains carrying other alleles of Itga4     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Itga4^tm1Mshi/Itga4^tm1Mshi

        C57BL/6-Itga4^tm1Mshi

• immune system phenotype
• abnormal leukocyte migration/homing (MGI Ref ID J:144092)
  • homing of lymphocytes into the gut is suppressed compared to in wild-type mice
  • in a DSS-induced model of colitis, homing of lymphocytes is reduced 50% compared to in similarly treated wild-type mice
• abnormal leukocyte adhesion (MGI Ref ID J:144092)
  • in cation conditions, the basal adhesiveness of lymphocytes is increased compared to in wild-type cells
  • despite normal rolling behavior, lymphocytes exhibit increased firm adhesion to Peyer patch venules compared to wild-type cells
• abnormal leukocyte transmigration (MGI Ref ID J:144092)
  • CXCL12-stimulated lymphocyte migration in the presence of transmigration inserts coated in VCAM1 or MAdCAM1 is reduced 50%, and exhibit reduced lateral migration compared to the migration of similarly treated wild-type cells
  • 50% fewer lymphocytes exhibit transendothelial migration under shear stress conditions of 2.0 dyne/cm² compared to similarly treated wild-type cells
• abnormal mononuclear leukocyte morphology (MGI Ref ID J:144092)
  • fewer mononuclear cells are present in the intraepithelial lymphocyte compartment and the Peyer's patches compared to in wild-type mice
• decreased lymphocyte cell number (MGI Ref ID J:144092)
  • mice exhibit a reduction in the number of lymphocytes in the gut (ei. Peyer's patches and intraepithelial lymphocyte compartments)
• decreased B cell number (MGI Ref ID J:144092)
  • fewer B220+ B cells are present in the intraepithelial lymphocyte compartment and the Peyer's patches compared to in wild-type mice
• decreased T cell number (MGI Ref ID J:144092)
  • fewer CD3+ T cells are present in the intraepithelial lymphocyte compartment and the Peyer's patches compared to in wild-type mice
• small Peyer's patches (MGI Ref ID J:144092)
• hematopoietic system phenotype
• abnormal mononuclear leukocyte morphology (MGI Ref ID J:144092)
  • fewer mononuclear cells are present in the intraepithelial lymphocyte compartment and the Peyer's patches compared to in wild-type mice
• decreased lymphocyte cell number (MGI Ref ID J:144092)
  • mice exhibit a reduction in the number of lymphocytes in the gut (ei. Peyer's patches and intraepithelial lymphocyte compartments)
• decreased B cell number (MGI Ref ID J:144092)
  • fewer B220+ B cells are present in the intraepithelial lymphocyte compartment and the Peyer's patches compared to in wild-type mice
• decreased T cell number (MGI Ref ID J:144092)
  • fewer CD3+ T cells are present in the intraepithelial lymphocyte compartment and the Peyer's patches compared to in wild-type mice

View Research Applications

Research Applications

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

Cell Biology Research
Defects in Cell Adhesion Molecules

Immunology and Inflammation Research
Lymphoid Tissue Defects
      B and T cell deficiency
      Lymphocyte Homing

Genes & Alleles

Gene & Allele Information

Allele Symbol		Itga4tm1Mshi
Allele Name		targeted mutation 1, Motomu Shimaoka
Allele Type		Targeted (knock-in)
Common Name(s)		Itga4-R/AGFFKR;
Mutation Made By		Motomu Shimaoka,   Immune Disease Institute (formerly CBRI)
Strain of Origin		C57BL/6
ES Cell Line Name		Bruce 4
ES Cell Line Strain		C57BL/6
Gene Symbol and Name		Itga4, integrin alpha 4
Chromosome		2
Gene Common Name(s)		CD49D; IA4; MGC90518; VLA-4 receptor, alpha 4 subunit;
Molecular Note		Exon 28 was replaced with one in which nucleotide substitutions resulted in amino acid substitutions of GFFKA for GFFKR. This sequence is involved in the formation of a membrane-proximal salt bridge necessary for inactivation. A self-excising neo cassette was inserted upstream of exon 28 and subsequently deleted in chimeras. [MGI Ref ID J:144092]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Imai Y; Park EJ; Peer D; Peixoto A; Cheng G; von Andrian UH; Carman CV; Shimaoka M. 2008. Genetic perturbation of the putative cytoplasmic membrane-proximal salt bridge aberrantly activates alpha(4) integrins. Blood 112(13):5007-15. [PubMed: 18809756]  [MGI Ref ID J:144092]

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

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location). This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - 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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fax:	207-288-6655

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