JAX
Mouse Strain Datasheet - 005308
B10.Cg-H2d Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ
Also Known As: clone 4 TCR
These transgenic mice express a T-cell receptor specific for an epitope of hemagglutinin that is restricted by MHC class I H2-Kd.
Donating Investigator
Linda Sherman, The Scripps Research Institute
Genetic overview
| Genetic Background | Generation |
|---|---|
|
000463 B10.D2-Hc1 H2d H2-T18c/nSnJ |
|
H2d
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Spontaneous | H2 | histocompatibility-2, MHC |
Hc1
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Not Applicable | Hc | hemolytic complement |
Tg(TcraCl4,TcrbCl4)1Shrm
| Allele Type |
|---|
| Transgenic (Inserted expressed sequence) |
Marker(s)
| Marker Symbol | Marker Name | |
|---|---|---|
| H2-T18 | histocompatibility 2, T region locus 18 |
Research Applications
- Immunology, Inflammation and Autoimmunity Research
- Research Tools
Detailed Description
Transgenic mice are viable, fertile, normal in size, normoglycemic and do not display any gross physical or behavioral abnormalities.The TCR expressed from this transgene is specific for influenza virus A/PR/8 hemagglutinin (HA) in the context of the MHC class I molecule H2-Kd. Both thymic and peripheral T-cell populations are skewed toward CD8+ cells. The majority of thymocytes and virtually all CD8+ T cells in lymph nodes express the transgenic TCR beta chain. About 40% of peripheral blood CD8+ T cells react with the HA peptide presented by H2-Kd. When mated with Tg(Ins2-HA)165Bri, double transgenic neonates have similar levels of V-beta 8 and total number of thymocytes as Tg(TcraCl4,TcrbCl4) mice however the double transgenics become spontaneously diabetic after birth and die within 10 days.
This transgenic model is useful in the study of T-cell activation, cross presentation of antigens, process of thymic selection, peripheral tolerance and the immune response to influenza.
Development
The Tcra and Tcrb transgenes encode a Tcr cDNA from Clone 4 derived from a B10.D2-Hc1 H2d H2-T18c/nSn mouse previously immunized with Influenza virus A/PR/8. The clone 4 transgenic constructs were co-injected and co-inserted in (C57BL/6 x BALB/c)F1 oocytes. Transgene positive mice were backcrossed to B10.D2-Hc1 H2d H2-T18c for 20 generations. In 2005, The Jackson Laboratory received B10.Cg-H2d Tg(TcraCl4,TcrbCl4)1Shrm/ShrmJ (Clone4 TCR) at generation N20 and backcrossed it to B10.D2-Hc1 H2d H2-T18c/nSnJ (Stock No. 000463) one generation prior to maintaining by brother-sister matings.
Expression Data
| Expressed Gene | Tcra, T cell receptor alpha chain, mouse, laboratory |
|---|---|
| Expressed Gene | Tcrb, T cell receptor beta chain, mouse, laboratory |
| Site of Expression | T-cells. |
Control Suggestions
Selected References
- Morgan DJ; Liblau R; Scott B; Fleck S; McDevitt HO; Sarvetnick N; Lo D; Sherman LA. 1996. CD8(+) T cell-mediated spontaneous diabetes in neonatal mice. J Immunol 157(3):978-83. PubMed: 8757600MGI: J:99756
H2d
Allele Symbol: H2d
| Allele Name | d variant |
|---|---|
| Allele Type | Spontaneous |
| Allele Synonym(s) | |
| Gene Symbol and Name | H2, histocompatibility-2, MHC |
| Gene Synonym(s) | H-2; H-2; MHC-II |
| Strain of Origin | various |
| Chromosome | 17 |
| General Note | The d variant has been observed in the following strains: DBA/2, DBA/2J BALB/c, BALB/cByJ, BALB/cJ, C57BLKS, NZB. |
Hc1
Allele Symbol: Hc1
| Allele Name | sufficient |
|---|---|
| Allele Type | Not Applicable |
| Allele Synonym(s) | C5 sufficient; C5-s; C5-suf |
| Gene Symbol and Name | Hc, hemolytic complement |
| Gene Synonym(s) | C5; C5; C5D; C5a; C5b; CPAMD4; ECLZB; He; He |
| Strain of Origin | Not Applicable |
| Chromosome | 2 |
| General Note | Hc was identified as a candidate gene for Abhr2 in a microarray analysis of lung mRNA from A/J, C3H/HeJ, and (A/J x C3H/HeJ)F1 x A/J backcross animals. Hc genotype shows statistically significant correlation to allergen-induced bronchial hyperresponsive phenotype. The C3H/HeJ allele does not have the 2 bp deletion and is associated with resistance to allergen-induced bronchial hyperresponsiveness. (J:108211) |
| Molecular Note | This allele does not contain the 2 base "TA" deletion found in the Hc0 allele and is found in the following mouse strains BALB/cJ, C57BL/6J, DBA/1J, and B10.D2/nSnJ. This is equivalent to the wild-type allele. |
Tg(TcraCl4,TcrbCl4)1Shrm
Allele Symbol: Tg(TcraCl4,TcrbCl4)1Shrm
| Allele Name | transgene insertion 1, Linda Sherman |
|---|---|
| Allele Type | Transgenic (Inserted expressed sequence) |
| Allele Synonym(s) | (HA)-TCR; C4; CL-4; CL-4 TCR; CL4; CL4-TCR; Clone 4; Clone-4 TCR; clone 4 TCR |
| Gene Symbol and Name | Tg(TcraCl4,TcrbCl4)1Shrm, transgene insertion 1, Linda Sherman |
| Gene Synonym(s) | (HA)-TCR; CL4; CL4-TCR; Clone 4; Clone-4 TCR; clone 4 TCR |
| Promoter | Tcra, T cell receptor alpha chain, mouse, laboratory |
| Promoter | Tcrb, T cell receptor beta chain, mouse, laboratory |
| Expressed Gene | Tcra, T cell receptor alpha chain, mouse, laboratory |
| Expressed Gene | Tcrb, T cell receptor beta chain, mouse, laboratory |
| Site of Expression | T-cells. |
| Strain of Origin | (C57BL/6 x BALB/c)F1 |
| Chromosome | UN |
| Molecular Note | Tcra and Tcrb cDNAs were isolated from Clone-4, a CTL line derived from a B10.D2-Hc1 H2d H2-t18c/nSnJ mouse immunized with influenza virus A/PR/8. A Tcra cDNA fragment representing the V-J exon, containing Valpha10, was cloned into a Tcra shuttle vector that includes a mouse Tcra-V promoter, the immunoglobulin heavy-chain enhancer EH, and the Tcra-C genes with some flanking DNA. Likewise, a Tcrb cDNA fragment representing the VDJ exon, containing Vbeta8.2, was cloned into a Tcrb shuttle vector including a mouse Tcrb-V promoter, EH, and the Tcrb-C genes with some flanking DNA. The plasmid constructs were coinjected. This transgenic TCR specifically recognizes influenza virus A/PR/8 hemagglutinin restricted by MHC class I H2kd. |
| Mutations Made By | Linda Sherman, The Scripps Research Institute |
H2-T18
Marker Symbol: H2-T18
| Marker Synonym(s) | H-2T18; H-2T18; TL Ag; Tla; Tla; thymus leukemia antigen |
|---|---|
| Chromosome(s) | 17 |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
- Immunology, Inflammation and Autoimmunity Research
- Rearranged Antigen-Specific T Cell Receptor Transgenes
- Research Tools
- Cancer Research
- tumor immunology
- Diabetes and Obesity Research
- Immunology, Inflammation and Autoimmunity Research
- T Cell Receptor Transgenics
- Cancer Research
Genotype: H2d related
- Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
Genotype: Hc1 related
- Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
- specific complement deficiency, control
- Immunodeficiency
- Research Tools
- Immunology, Inflammation and Autoimmunity Research
- specific complement deficiency, C5 complement, control
- Immunology, Inflammation and Autoimmunity Research
Mammalian Phenotype Terms by Genotype
Genotype: Tg(TcraCl4,TcrbCl4)1Shrm/?
B10.Cg-H2d Tg(TcraCl4,TcrbCl4)1Shrm
immune system phenotype
- abnormal CD8-positive, alpha-beta T cell differentiation
- 40% of the CD8 T cells in the blood are reactive to HA peptide presented by H2-Kd (MGI Ref ID J:99756)
- most thymocytes also express the transgenic TCR (MGI Ref ID J:99756)
- the majority of mature CD8 T cells in the periphery express the transgenic T cell receptor (TCR) that is specific for influenza virus hemagglutinin (HA) peptide presented by MHC-Class I H2-Kd (MGI Ref ID J:99756)
- abnormal T cell subpopulation ratio
hematopoietic system phenotype
- abnormal CD8-positive, alpha-beta T cell differentiation
- 40% of the CD8 T cells in the blood are reactive to HA peptide presented by H2-Kd (MGI Ref ID J:99756)
- most thymocytes also express the transgenic TCR (MGI Ref ID J:99756)
- the majority of mature CD8 T cells in the periphery express the transgenic T cell receptor (TCR) that is specific for influenza virus hemagglutinin (HA) peptide presented by MHC-Class I H2-Kd (MGI Ref ID J:99756)
References
- Morgan DJ; Liblau R; Scott B; Fleck S; McDevitt HO; Sarvetnick N; Lo D; Sherman LA. 1996. CD8(+) T cell-mediated spontaneous diabetes in neonatal mice. J Immunol 157(3):978-83. PubMed: 8757600MGI: J:99756
Additional - H2d related
- Addis-Lieser E; Kohl J; Chiaramonte MG. 2005. Opposing regulatory roles of complement factor 5 in the development of bleomycin-induced pulmonary fibrosis. J Immunol 175(3):1894-902. PubMed: 16034133MGI: J:107269
- Bakir HY; Tomiyama-Miyaji C; Watanabe H; Nagura T; Kawamura T; Sekikawa H; Abo T. 2006. Reasons why DBA/2 mice are resistant to malarial infection: expansion of CD3int B220+ gammadelta T cells with double-negative CD4- CD8- phenotype in the liver. Immunology 117(1):127-35. PubMed: 16423048MGI: J:106141
- Bassi EJ; Moraes-Vieira PM; Moreira-Sa CS; Almeida DC; Vieira LM; Cunha CS; Hiyane MI; Basso AS; Pacheco-Silva A; Camara NO. 2012. Immune regulatory properties of allogeneic adipose-derived mesenchymal stem cells in the treatment of experimental autoimmune diabetes. Diabetes 61(10):2534-45. PubMed: 22688334MGI: J:208536
- Bhadra S; Lozano MM; Payne SM; Dudley JP. 2006. Endogenous MMTV Proviruses Induce Susceptibility to Both Viral and Bacterial Pathogens. PLoS Pathog 2(12):e128. PubMed: 17140288MGI: J:120299
- Bode J; Dutow P; Sommer K; Janik K; Glage S; Tummler B; Munder A; Laudeley R; Sachse KW; Klos A. 2012. A new role of the complement system: C3 provides protection in a mouse model of lung infection with intracellular Chlamydia psittaci. PLoS One 7(11):e50327. PubMed: 23189195MGI: J:194784
- Buhlmann JE; Gonzalez M; Ginther B; Panoskaltsis-Mortari A; Blazar BR; Greiner DL; Rossini AA; Flavell R; Noelle RJ. 1999. Cutting edge: sustained expansion of CD8+ T cells requires CD154 expression by Th cells in acute graft versus host disease. J Immunol 162(8):4373-6. PubMed: 10201970MGI: J:119788
- Casati A; Frascoli M; Traggiai E; Proietti M; Schenk U; Grassi F. 2011. Cell-autonomous regulation of hematopoietic stem cell cycling activity by ATP. Cell Death Differ 18(3):396-404. PubMed: 20798687MGI: J:186980
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- Reed-Loisel LM; Sullivan BA; Laur O; Jensen PE. 2005. An MHC class Ib-restricted TCR that cross-reacts with an MHC class Ia molecule. J Immunol 174(12):7746-52. PubMed: 15944277MGI: J:109978
- Rodrigues OR; Moura RA; Gomes-Pereira S; Santos-Gomes GM. 2006. H-2 complex influences cytokine gene expression in Leishmania infantum-infected macrophages. Cell Immunol 243(2):118-26. PubMed: 17316586MGI: J:120728
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- Schmitt J; Roderfeld M; Sabrane K; Zhang P; Tian Y; Mertens JC; Frei P; Stieger B; Weber A; Mullhaupt B; Roeb E; Geier A. 2012. Complement factor C5 deficiency significantly delays the progression of biliary fibrosis in bile duct-ligated mice. Biochem Biophys Res Commun 418(3):445-50. PubMed: 22277671MGI: J:181268
- Sho M; Yamada A; Najafian N; Salama AD; Harada H; Sandner SE; Sanchez-Fueyo A; Zheng XX; Strom TB; Sayegh MH. 2002. Physiological mechanisms of regulating alloimmunity: cytokines, CTLA-4, CD25+ cells, and the alloreactive T cell clone size. J Immunol 169(7):3744-51. PubMed: 12244168MGI: J:120408
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Additional - Hc1 related
- Actor JK; Breij E; Wetsel RA; Hoffmann H; Hunter RL Jr; Jagannath C. 2001. A role for complement C5 in organism containment and granulomatous response during murine tuberculosis. Scand J Immunol 53(5):464-74. PubMed: 11309154MGI: J:103981
- Addis-Lieser E; Kohl J; Chiaramonte MG. 2005. Opposing regulatory roles of complement factor 5 in the development of bleomycin-induced pulmonary fibrosis. J Immunol 175(3):1894-902. PubMed: 16034133MGI: J:107269
- Bode J; Dutow P; Sommer K; Janik K; Glage S; Tummler B; Munder A; Laudeley R; Sachse KW; Klos A. 2012. A new role of the complement system: C3 provides protection in a mouse model of lung infection with intracellular Chlamydia psittaci. PLoS One 7(11):e50327. PubMed: 23189195MGI: J:194784
- Girardi G; Berman J; Redecha P; Spruce L; Thurman JM; Kraus D; Hollmann TJ; Casali P; Caroll MC; Wetsel RA; Lambris JD; Holers VM; Salmon JE. 2003. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J Clin Invest 112(11):1644-54. PubMed: 14660741MGI: J:86845
- Howell GR; Soto I; Ryan M; Graham LC; Smith RS; John SW. 2013. Deficiency of complement component 5 ameliorates glaucoma in DBA/2J mice. J Neuroinflammation 10(1):76. PubMed: 23806181MGI: J:199369
- Jackson HM; Onos KD; Pepper KW; Graham LC; Akeson EC; Byers C; Reinholdt LG; Frankel WN; Howell GR. 2015. DBA/2J genetic background exacerbates spontaneous lethal seizures but lessens amyloid deposition in a mouse model of Alzheimer's disease. PLoS One 10(5):e0125897. PubMed: 25933409MGI: J:227541
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