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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote (Female x Male) Species laboratory mouse Generation N12+N110 (13-OCT-08) Donating Investigator Sergei Nedospasov, NCI-FCRDC 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. No gene product (mRNA) from any of the three targeted genes is detected by RT-PCR analysis of concanavalin-A activated splenocytes. Leukocyte numbers in the spleen, blood and peritoneal cavity are increased 2 to 3 fold. Homozygous mice have abnormal lymphoid development and do not develop Peyer's patches or lymph nodes. Spleen microarchitecture is abnormal. No germinal center forms in the spleen following antigenic challenge. Mutant mice display defective antibody responses. This strain displays a phenotype more severe than the phenotypes exhibited by any of the single targeted mutation strains of the genes and may be useful in studies of peripheral lymphoid organ development, and antibody response to T cell dependent antigens.Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes, and four loxP sites, flanking each of the three genes, was used to disrupt 8.4 kb of sequence encoding all of the Tnf gene and the last exons of the Lta and Ltb genes. The construct was electroporated into 129P2/OlaHsd derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a cre expression plasmid for the purpose of removing the selectable marker cassette. ES cells that had successfully undergone Cre-mediated recombination and no longer retained the cassette were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to for 12 generations.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Lta
002258 B6.129S2-Ltatm1Dch/J 002257 B6;129S2-Ltatm1Dch/J 005579 C57BL/6J-Ltahlb382/J View Strains carrying other alleles of Lta (3 strains)
003530 B6;129-Ltbtm1Flv/J 005112 STOCK Ltb/Tnftm1.1Dvk/J
005540 B6.129S-Tnftm1Gkl/J 003008 B6;129S-Tnftm1Gkl/J 007082 CByJ.129S(B6)-Tnftm1Gkl/J 005112 STOCK Ltb/Tnftm1.1Dvk/J
Additional Web Information
Congenic Nomenclature
Phenotype
Phenotype Information
assigned by genotype
Ltb/Tnf/Ltatm1Dvk/Ltb/Tnf/Ltatm1Dvk
involves: C57BL/6
- hematopoietic system phenotype
- decreased spleen white pulp amount (MGI Ref ID J:109621)
- percentage of splenic white pulp is lower than in wild-type, Ltb, the two Lta mutant lines, Ltb or Ltbr knockouts
- immune system phenotype
- decreased spleen white pulp amount (MGI Ref ID J:109621)
- percentage of splenic white pulp is lower than in wild-type, Ltb, the two Lta mutant lines, Ltb or Ltbr knockouts
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Ltb/Tnf/Ltatm1Dvk | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Dmitry V Kuprash | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | TNF/LTDelta3; | ||
| Mutation Made By | Dmitry Kuprash, Engelhardt Inst of Molecular Biology | ||
| Gene Symbol and Name | Lta, lymphotoxin A | ||
| Chromosome | 17 | ||
| Gene Common Name(s) | LT; LT-[a]; LT-alpha; LT[a]; LTalpha; Ltx; TNF beta; TNF-beta; TNFB; TNFSF1; Tnfb; Tnfsf1b; heart, lung and blood 382; hlb382; lymphotoxin; lymphotoxin alpha; tumor necrosis factor beta; | ||
| Molecular Note | An 8.4 kb region, containing the entire Tnf gene and the last coding exons of the Lta and Ltb genes, was deleted by cre mediated recombination of surrounding loxP sites inserted within Lta and Ltb via homologous recombiantion. Partial coding regions of Lta and Ltb were left intact separtated by a single loxP site, however RT-PCR analysis of homozygous mutant splenocytes activated by concanavalin A indicated an absence of transcript from each locus. [MGI Ref ID J:80616] | ||
| Gene Symbol and Name | Tnf, tumor necrosis factor | ||
| Chromosome | 17 | ||
| Gene Common Name(s) | DIF; MGC124630; RATTNF; TNF alpha; TNF-alpha; TNFA; TNFSF2; TNFalpha; Tnfa; Tnfsf1a; tumor necrosis factor, alpha; tumor necrosis factor-alpha; | ||
| Gene Symbol and Name | Ltb, lymphotoxin B | ||
| Chromosome | 17 | ||
| Gene Common Name(s) | AI662801; LTbeta; MGC108924; TNFC; TNFSF3; Tnfc; expressed sequence AI662801; lymphotoxin beta; p33; tumor necrosis factor C; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Ltb/Tnf/Ltatm1Dvk, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Kuprash DV; Alimzhanov MB; Tumanov AV; Grivennikov SI; Shakhov AN; Drutskaya LN; Marino MW; Turetskaya RL; Anderson AO; Rajewsky K; Pfeffer K; Nedospasov SA. 2002. Redundancy in tumor necrosis factor (TNF) and lymphotoxin (LT) signaling in vivo: mice with inactivation of the entire TNF/LT locus versus single-knockout mice. Mol Cell Biol 22(24):8626-34. [PubMed: 12446781] [MGI Ref ID J:80616]
Additional References
Ltb/Tnf/Ltatm1Dvk relatedBaseta JG; Stutman O. 2000. TNF regulates thymocyte production by apoptosis and proliferation of the triple negative (CD3-CD4-CD8-) subset. J Immunol 165(10):5621-30. [PubMed: 11067918] [MGI Ref ID J:112282]
Liepinsh DJ; Grivennikov SI; Klarmann KD; Lagarkova MA; Drutskaya MS; Lockett SJ; Tessarollo L; McAuliffe M; Keller JR; Kuprash DV; Nedospasov SA. 2006. Novel lymphotoxin alpha (LTalpha) knockout mice with unperturbed tumor necrosis factor expression: reassessing LTalpha biological functions. Mol Cell Biol 26(11):4214-25. [PubMed: 16705172] [MGI Ref ID J:109621]
Rebholz B; Haase I; Eckelt B; Paxian S; Flaig MJ; Ghoreschi K; Nedospasov SA; Mailhammer R; Debey-Pascher S; Schultze JL; Weindl G; Forster I; Huss R; Stratis A; Ruzicka T; Rocken M; Pfeffer K; Schmid RM; Rupec RA. 2007. Crosstalk between Keratinocytes and Adaptive Immune Cells in an IkappaBalpha Protein-Mediated Inflammatory Disease of the Skin. Immunity 27(2):296-307. [PubMed: 17692539] [MGI Ref ID J:124343]
Tumanov AV; Kuprash DV; Mach JA; Nedospasov SA; Chervonsky AV. 2004. Lymphotoxin and TNF produced by B cells are dispensable for maintenance of the follicle-associated epithelium but are required for development of lymphoid follicles in the Peyer's patches. J Immunol 173(1):86-91. [PubMed: 15210762] [MGI Ref ID J:90815]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry These mice are considered immunocompromised; SPF conditions are recommended. Mating System Homozygote x Homozygote (Female x Male) Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $155.60 Female or Male Homozygous for Ltb/Tnf/Ltatm1Dvk *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $311.20 Homozygous for Ltb/Tnf/Ltatm1Dvk x Homozygous for Ltb/Tnf/Ltatm1Dvk
Additional Supply Details
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $202.30 Female or Male Homozygous for Ltb/Tnf/Ltatm1Dvk *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $404.60 Homozygous for Ltb/Tnf/Ltatm1Dvk x Homozygous for Ltb/Tnf/Ltatm1Dvk
Additional Supply Details
| Supply Notes |
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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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. | ||
General Terms and Conditions
See Terms of Use
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.Ordering and Purchasing Information
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Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.
Contact information
General inquiries
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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