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Type Mutant Strain; Transgenic; Species laboratory mouse Generation N?+10 Donating Investigator Jeffrey Rosen, Baylor College of Medicine Description
The FVB/N-TgN(Trp53R172L)4491Jmr express TRP53 with pseudo-wildtype properties capable of inducing p21 and mdm-2 expression. Lobuloalveolar development is altered and apoptosis is increased during late pregnancy. The few normal lobules observed during early lactation did not express the Trp53 transgene suggesting that they arose by clonal expansion of cells not expressing the transgene during mid-pregnancy. Transgenic mice fail to lactate. There is no apparent alteration in ductal development. Mice expressing a dominant negative 172Arg-His mutation do not exhibit any detectable alterations in mammary gland development and have a very low incidence of spontaneous mammary tumors. Mice bearing the 172Arg-Leu transgene and a pituitary isograft displayed a marked increase in apoptosis and a significant delay in DMBA-induced tumorigenesis, while those bearing the 172Arg-His dominant negative p53 transgene were more susceptible to DMBA-induced tumorigenesis.
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Trp53
004301 129-Trp53tm1Holl/J 002080 129-Trp53tm1Tyj/J 002101 B6.129S2-Trp53tm1Tyj/J 007218 B6.129S6-Trp53tm2Xu/J 007962 B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J 006980 B6;129-Trp53tm2Xu/J 008191 B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J 002103 B6;129S2-Trp53tm1Tyj/J 002526 C.129S2(B6)-Trp53tm1Tyj/J 002547 C3Ou.129S2(B6)-Trp53tm1Tyj/J 002899 FVB.129S2(B6)-Trp53tm1Tyj/J 002659 FVB/N-Tg(Trp53R172H)8512Jmr/J 003262 STOCK Tg(Trp53A135V)L3Ber/J View Strains carrying other alleles of Trp53 (13 strains)
Strains carrying other alleles of Wap
007962 B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J 002499 C57BL/6J-Tg(WapIGFBP3)67Dlr/J 002659 FVB/N-Tg(Trp53R172H)8512Jmr/J View Strains carrying other alleles of Wap (3 strains)
Mammalian Phenotype Terms assigned by genotype
Tg(Trp53R172L)4491Jmr/0
FVB/N-Tg(Trp53R172L)4491Jmr
- reproductive system phenotype
- abnormal mammary gland growth during lactation (MGI Ref ID J:56433)
- during lactation, mammary glands exhibit incomplete development with few normal lobuloalveolar structures compared to in wild-type mice
- abnormal mammary gland physiology (MGI Ref ID J:56433)
- mice exhibit increased mammary gland cell sensitivity to radiation induced apoptosis compared to in similarly treated wild-type mice
- abnormal lactation (MGI Ref ID J:56433)
- females fail to lactate resulting in reduced pup weight and increased pup mortality
- skin/coat/nails phenotype
- abnormal hair follicle morphology (MGI Ref ID J:56433)
- mice exhibit follicular dilatation and comedo formation
- skin lesions (MGI Ref ID J:56433)
- lesions in the hind quarter represent follicular dilatation and comedo formation
- tumorigenesis
- *normal* tumorigenesis (MGI Ref ID J:56433)
- despite expression of the transgene, mice do not exhibit an increase in spontaneous tumor rates
- endocrine/exocrine gland phenotype
- abnormal mammary gland growth during lactation (MGI Ref ID J:56433)
- during lactation, mammary glands exhibit incomplete development with few normal lobuloalveolar structures compared to in wild-type mice
- abnormal mammary gland physiology (MGI Ref ID J:56433)
- mice exhibit increased mammary gland cell sensitivity to radiation induced apoptosis compared to in similarly treated wild-type mice
- abnormal lactation (MGI Ref ID J:56433)
- females fail to lactate resulting in reduced pup weight and increased pup mortality
Tg(Trp53R172L)4491Jmr/0
involves: FVB/N
- reproductive system phenotype
- abnormal mammary gland growth during lactation (MGI Ref ID J:101547)
- by day 2 of lactation following gamma irradiation, few normal lobuloalveolar structures are detected unlike in wild-type mice due to increased apoptosis
- pituitary engrafts increase apoptosis by 10-fold and the disruption of lobuloalveolar structures observed during lactation
- tumorigenesis
- decreased incidence of chemically-induced tumors (MGI Ref ID J:101547)
- following pituitary engrafts and exposure to DMBA, mice exhibit reduced induction rates and tumor burden of mammary tumors compared to similarly treated wild-type mice
- both squamous adenocarcinomas (early developing) and type B mammary adenocarcinomas (late developing) are induced by DMBA treatment of mice with pituitary engrafts unlike in similarly treated wild-type mice, which mainly develop squamous adenocarcinomas
- however, DMBA treated mice that do not receive pituitary engrafts exhibit normal tumorigenesis
- endocrine/exocrine gland phenotype
- abnormal mammary gland growth during lactation (MGI Ref ID J:101547)
- by day 2 of lactation following gamma irradiation, few normal lobuloalveolar structures are detected unlike in wild-type mice due to increased apoptosis
- pituitary engrafts increase apoptosis by 10-fold and the disruption of lobuloalveolar structures observed during lactation
Research Applications
This mouse can be used to support research in many areas including:
Trp53 relatedCancer Research
Genes Regulating Growth and Proliferation
Apoptosis Research
Endogenous Regulators
Cancer Research
Increased Tumor Incidence (Lymphomas)
Increased Tumor Incidence (Other Tissues/Organs: osteosarcoma)
Toxicology
Tumor Suppressor Genes
Immunology and Inflammation Research
Intracellular Signaling Molecules
Mouse/Human Gene Homologs
Li-Fraumeni syndrome
Research Tools
Toxicology Research (B and T cell deficiency) (xenograft transplant host)
Toxicology Research (drug/compound testing)
| Allele Symbol | Tg(Trp53R172L)4491Jmr | ||
|---|---|---|---|
| Allele Name | transgene insertion 4491, Jeffrey Rosen | ||
| Mutation Made By | Jeffrey Rosen, Baylor College of Medicine | ||
| Strain of Origin | FVB | ||
| Expressed Gene | Trp53, transformation related protein 53, mouse, laboratory | ||
| Promoter | Wap, whey acidic protein, rat | ||
| Molecular Note | This transgene contains the rat whey acidic protein promoter (0.95 kb of 5' sequence) fused to a mouse Trp53 minigene that carries a transversion in codon 172 (CGC->CTC; "Arg172Leu"). Removal of the ts mutation in the original Trp53 minigene at codon 135(Ala-Val) and introduction of the Arg-Leu mutation at amino acid 172 were accomplished using recombinant PCR mutagenesis. [MGI Ref ID J:56433] | ||
Genotyping Protocols
Tg(Trp53R172_), STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
Li B; Greenberg N; Stephens LC; Meyn R; Medina D; Rosen JM. 1994. Preferential overexpression of a 172Arg-->Leu mutant p53 in the mammary gland of transgenic mice results in altered lobuloalveolar development. Cell Growth Differ 5(7):711-21. [PubMed: 7947386] [MGI Ref ID J:56433]
Tg(Trp53R172L)4491Jmr related
Li B; Kittrell FS; Medina D; Rosen JM. 1995. Delay of dimethylbenz[a]anthracene-induced mammary tumorigenesis in transgenic mice by apoptosis induced by an unusual mutant p53 protein. Mol Carcinog 14(2):75-83. [PubMed: 7576102] [MGI Ref ID J:101547]
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
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| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| 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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