Strain Name:

B6.FVB-Tg(CD46)2Gsv/J

Stock Number:

004971

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Availability:

Cryopreserved - Ready for recovery

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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 B6.FVB-Tg(CD46)2Olds/J    (Changed: 27-NOV-06 )
B6.FVB-Tg(MCP)2Olds/J    (Changed: 02-OCT-06 )
Type Congenic; Mutant Strain; Transgenic;
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Specieslaboratory mouse
 
Donating InvestigatorDr. Michael B.A. Oldstone,   The Scripps Research Institute

Description
These mice carry the YAC-CD46 transgene coding for the human CD46 protein (also known as MCP), which serves as the receptor for the human measles virus, group B adenoviruses, the human herpes simplex VI virus and Neisseria gonorrhoeae. The expression of this transgene is under the direction of the human CD46 promoter. Transgene expression is detected by in situ hybridization examination of whole animal sections, by Northern blot analysis of brain, spleen, lymph nodes, thymus, kidney, liver, gut and lung, and by FACS analysis of CD4+/CD8+ lymphocytes. Levels of transgenic protein on cell surfaces are similar to levels found in human cells. This line carries 10 to 12 copies of the transgene. Transgenic mice are susceptible to measles virus (MV) infection, expressing MV antigens and releasing infectious viral particles. The spread of the virus throughout the nervous system and the suppression of the immune system mimic the course of MV infection in humans. Transgenic mice infected with MV exhibit reduced numbers of macrophages, neutrophils and IFN-gamma producing T-cells, and are more susceptible to Listeria monocytogenes bacteria infection. Mice that are homozygous for the targeted mutation are viable and fertile. This mutant mouse strain may be useful in the study of pathogenesis and treatment of microbial infections by the various viruses that are able to utilize CD46/MCP as a receptor.

Development
The YAC-CD46 transgene (containing a full-length human CD46 gene (also called MCP)) was injected into FVB/N pronuclei. Founder animals (line 2) were bred to C57BL/6 mice. The strain has been backcrossed for 12 generations on the C57BL/6 background (October 2003).

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.
Hemolytic Uremic Syndrome, Atypical, Susceptibility to, 2; AHUS2   (CD46)
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.

Tg(CD46)2Gsv/0

        involves: C57BL/6 * FVB/N
  • mortality/aging
  • premature death
    • 94% of transgenic mice (mortality of all transgenics is similar, regardless of background) die within 3 weeks of infection (regardless of background), but no non-transgenic littermates become ill   (MGI Ref ID J:109895)
  • immune system phenotype
  • abnormal cell-mediated immunity
    • infected transgenic mice that were primed with LCMV virus 60-90 days earlier can not mount an MHC-restricted cytotoxic T lymphocyte response to LCMV-infected targets   (MGI Ref ID J:109895)
    • defective cytotoxic T cell cytolysis
      • cytotoxic T cells can only lyse LCMV-infected MHC class I but not class II targets   (MGI Ref ID J:109895)
  • abnormal chemokine level
    • CC chemokines (RANTES, MIP-alpha and -beta, and MCP-1) and CXC chemokines (IP-10 and TCA-3, or MIG) are detected in brains of infected mice but EOTXN, LTN and MIP-2 are not   (MGI Ref ID J:109895)
  • abnormal cytokine secretion
    • at 6 days postinfection, a 6-fold increase in Il-12 expression (RNA), an 11-fold increase in lymphotoxin-beta and a 17-fold increase in TNFalpha expression are detected in brains of transgenic mice   (MGI Ref ID J:109895)
  • abnormal humoral immune response
    • humoral immune response is suppressed in infected transgenic mice; no antibody response to sheep red blood cells is generated while transgenic mice inoculated with vehicle instead of MV generated a significant antibody response   (MGI Ref ID J:109895)
  • abnormal response to transplant
    • transplanted hearts expressing the transgene slow down initially upon human serum perfusion, but recover while non-transgenic hearts (8/8) cease beating entirely   (MGI Ref ID J:113644)
  • increased susceptibility to viral infection
    • multiple cell types from transgene-expressing mice, including transgenic mice on varios other mixed or congenic backgrounds can be infected with measles virus (MV); cells become infected, express virus antigens, and release infectious viral progeny when cocultivated with permissive Vero cells (African green monkey kidney epithelial) compared to wild-type mouse cells   (MGI Ref ID J:109895)
    • neurons and lymphoid cells in the blood, spleen and lymph nodes express viral proteins and RNA upon injection of 103 pfu; in spleen and lymph nodes, MV is expressed primarily in T cell-enriched areas whereas cells from non-transgenic mice don't express viral proteins   (MGI Ref ID J:109895)
  • cardiovascular system phenotype
  • abnormal heart morphology
    • transgenic and normal hearts develop white discoloration upon slowing or cessation of heart beat after normal human serum perfusion, but transgenic hearts resume beating and normal coloration within 15 minutes   (MGI Ref ID J:113644)
    • 7/10 transgenic hearts resume functioning after ~3-5 minutes and begin beating normally within 15 minutes   (MGI Ref ID J:113644)
  • decreased heart rate
    • heart rate of transgenic hearts perfused with normal human serum after transplantion slows down similar to normal hearts perfused with decomplemented human serum; all non transgenic hearts perfused with normal human serum slow down immediately, resulting in white discoloration and complete cessation of heart beat within 3-5 minutes   (MGI Ref ID J:113644)
  • nervous system phenotype
  • abnormal neuron morphology
    • viral proteins and RNA are expressed in the CNS after inoculation; numerous MV nucleocapsids are present in neurons in optic tegmentum, cerebral cortex, hippocampus and cerebellum, moving into axons with normal and disorganized microtubules   (MGI Ref ID J:109895)
  • astrocytosis
    • generalized astrocytosis accompanies MV replication and spread, with infiltration of CD4+ and some CD8+ T cells into the brain parenchyma   (MGI Ref ID J:109895)
  • increased neuron apoptosis
    • MV-infected transgenic mice have 50 to 100-fold more apoptotic primary neurons than innoculated non-transgenic mice or transgenic mice that received a needle wound in the brain   (MGI Ref ID J:109895)
  • homeostasis/metabolism phenotype
  • abnormal chemokine level
    • CC chemokines (RANTES, MIP-alpha and -beta, and MCP-1) and CXC chemokines (IP-10 and TCA-3, or MIG) are detected in brains of infected mice but EOTXN, LTN and MIP-2 are not   (MGI Ref ID J:109895)
  • cellular phenotype
  • increased neuron apoptosis
    • MV-infected transgenic mice have 50 to 100-fold more apoptotic primary neurons than innoculated non-transgenic mice or transgenic mice that received a needle wound in the brain   (MGI Ref ID J:109895)
  • hematopoietic system phenotype
  • defective cytotoxic T cell cytolysis
    • cytotoxic T cells can only lyse LCMV-infected MHC class I but not class II targets   (MGI Ref ID J:109895)
View Research Applications

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

Research Tools
Immunology, Inflammation and Autoimmunity Research
      genes regulating susceptibility to infectious disease and endotoxin

Virology Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Tg(CD46)2Gsv
Allele Name transgene insertion 2, Frank Grosveld
Allele Type Transgenic (random, expressed)
Common Name(s) MCP YAC; MCP-YAC line 2; MY II; Tg(CD46)2Olds; Tg(MCP)Olds2; YAC CD46 line 2; YAC-CD46;
Mutation Made By Nikos Yannoutsos,   Innsbruck Medical University
Strain of OriginFVB/N
Expressed Gene CD46, CD46 molecule, complement regulatory protein, human
Promoter CD46, CD46 molecule, complement regulatory protein, human
Molecular Note The transgene comprises a partially intact, approximately 420-kb yeast artificial chromosome (YAC) from the Imperial Cancer Research Fund (ICRF, London, UK), designatied AM2: 6C10, that contains the complete human CD46/MCP gene including its 5' and 3' flanking regions. The genome of transgenic mice of line MY II contains 10-12 intact copies of CD46. The expected 4.5 - 4.8-kb transcript, as well as several smaller RNAs, are expressed at high levels in all tissues examined from transgenic mice. Immunohistochemistry likewise detects patterns of expression of human CD46 protein in transgenic mouse tissues similar to those in human tissues. FACS analysis detects CD46 on transgenic spleen cells at approximately 10-fold higher levels than on human splenocytes. [MGI Ref ID J:113644]
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(CD46)2Gsv, Melt Curve Analysis
Tg(CD46)2Gsv, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Oldstone MB; Lewicki H; Thomas D; Tishon A; Dales S; Patterson J; Manchester M; Homann D; Naniche D; Holz A. 1999. Measles virus infection in a transgenic model: virus-induced immunosuppression and central nervous system disease. Cell 98(5):629-40. [PubMed: 10490102]  [MGI Ref ID J:109895]

Yannoutsos N; Ijzermans JN; Harkes C; Bonthuis F; Zhou CY; White D; Marquet RL; Grosveld F. 1996. A membrane cofactor protein transgenic mouse model for the study of discordant xenograft rejection. Genes Cells 1(4):409-19. [PubMed: 9135084]  [MGI Ref ID J:113644]

Additional References

Tg(CD46)2Gsv related

Oldstone MB; Dales S; Tishon A; Lewicki H; Martin L. 2005. A role for dual viral hits in causation of subacute sclerosing panencephalitis. J Exp Med 202(9):1185-90. [PubMed: 16260490]  [MGI Ref ID J:118755]

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 & HusbandryThis strain originated on an FVB/N background and was backcrossed for 12 generations on the C57BL/6 background (October 2003). The strain is maintained as a hemizygote. SPF conditions are recommended.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2085.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. 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. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 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).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2710.50
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. 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. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 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).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Noncarrier
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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