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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
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; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator Michael 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 | ||
Additional Web Information
Congenic Nomenclature
Genetic Quality Control Annual Report
Phenotype
Phenotype Information
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
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
- life span-post-weaning/aging
- premature death (MGI Ref ID J:109895)
- 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
- immune system phenotype
- abnormal cell-mediated immunity (MGI Ref ID J:109895)
- 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
- defective cytotoxic T cell cytolysis (MGI Ref ID J:109895)
- cytotoxic T cells can only lyse LCMV-infected MHC class I but not class II targets
- abnormal chemokine physiology (MGI Ref ID J:109895)
- 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
- abnormal cytokine secretion (MGI Ref ID J:109895)
- 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
- abnormal humoral immune response (MGI Ref ID J:109895)
- 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
- abnormal response to transplant (MGI Ref ID J:113644)
- transplanted hearts expressing the transgene slow down initially upon human serum perfusion, but recover while non-transgenic hearts (8/8) cease beating entirely
- increased susceptibility to viral infection (MGI Ref ID J:109895)
- 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
- 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
- cardiovascular system phenotype
- abnormal heart morphology (MGI Ref ID J:113644)
- 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
- 7/10 transgenic hearts resume functioning after ~3-5 minutes and begin beating normally within 15 minutes
- decreased heart rate (MGI Ref ID J:113644)
- 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
- nervous system phenotype
- abnormal neuron morphology (MGI Ref ID J:109895)
- 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
- increased neuron apoptosis (MGI Ref ID J:109895)
- 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
- astrocytosis (MGI Ref ID J:109895)
- generalized astrocytosis accompanies MV replication and spread, with infiltration of CD4+ and some CD8+ T cells into the brain parenchyma
This mouse can be used to support research in many areas including:
Research Tools
Immunology and Inflammation Research (genes regulating susceptibility to infectious disease and endotoxin)
Virology Research
Genes & Alleles
Gene & Allele Information
| 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 | ||
| 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, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
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 relatedOldstone 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
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry This 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.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
Additional Supply Details
| Pricing for International shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 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. | ||
General Terms and Conditions
See Terms of Use
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