|In these p53LSL-25,26,53,54 mice both transactivation domains can be inactivated; expression of the mutant TRP53 protein is silenced until Cre recombinase mediates excision of the upstream floxed STOP cassette. These mice may be useful in studies of p53 function and the role of p53 as a transcriptional activator in tumor suppression.|
Type Coisogenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator Laura Attardi, Stanford University Medical Center
The Trp53, transformation related protein 53, gene encodes the p53 tumor suppressor protein, which functions as a transcription factor regulating expression of more than 100 target genes. Mutations resulting in inactivation of p53 protein facilitates tumor progression. These p53LSL-25,26,53,54 mice carry point mutations that result in the amino acid substitutions L25Q and W26S in exon 2, which encodes the first transcriptional activation domain of the protein, F53Q;F54S point mutation in exon 4, in the second transcriptional activation domain and a floxed STOP cassette upstream of exon 2. Expression of the mutant TRP53 protein is silenced until Cre recombinase mediates excision of the floxed STOP cassette. After Cre recombinase mediated removal of the floxed STOP cassette cells from the resulting mice express p53 protein with both transactivation domains inactivated, which cannot activate p53 target genes. Mice carrying the recombined allele exhibit defective cell cycle arrest or apoptosis activity in response to acute DNA damage and fail to suppress tumor development. When bred to Cre recombinase expressing mice, these mice could be used to generate tumor cells for engraftment experiments. Mice that are homozygous for the targeted mutation are viable, but have decreased fertility.
For example, when bred to B6.129-Gt(ROSA)26Sortm1(cre/ERT2)Tyj/J mice (Stock No. 008463) tamoxifen induced Cre recombinase expression in offspring reduces apoptosis following radiation treatment.
A targeting vector designed by Dr. Laura D. Attardi (Stanford University School of Medicine) containing a floxed STOP element with 4 poly adenylation sites, and a puromycin resistance cassette, was utilized to insert the floxed STOP cassette upstream of exon 2, the L25Q and W26S mutations into exon 2, and the F53Q;F54S point mutations into exon 4. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to 129 Sv/J mice. Upon arrival at The Jackson Laboratory, the mice were crossed to 129S1/SvImJ (Stock No. 002448) at least once to establish the colony.
|Wild-type from the colony|
|Considerations for Choosing Controls|
Strains carrying other alleles of Trp53
022070 129-Trp53tm1Att/J 004301 129-Trp53tm1Holl/J 002080 129-Trp53tm1Tyj/J 018431 129-Trp53tm3Att/J 008652 129S-Trp53tm2Tyj/J 008651 129S-Trp53tm3Tyj/J 008462 B6.129P2-Trp53tm1Brn/J 002101 B6.129S2-Trp53tm1Tyj/J 008183 B6.129S4(Cg)-Trp53tm2.1Tyj/J 008182 B6.129S4-Trp53tm3.1Tyj/J 007218 B6.129S6-Trp53tm2Xu/J 011109 B6.Cg-Trp53tm2Glo/Kvm 017767 B6;129-Trp53tm1.1Dgk/J 008045 B6;129-Trp53tm2Holl/J 006980 B6;129-Trp53tm2Xu/J 008191 B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J 002103 B6;129S2-Trp53tm1Tyj/J 008181 B6;129S4-Trp53tm4Tyj/J 008361 B6;129S4-Trp53tm5Tyj/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 002660 FVB/N-Tg(Trp53R172L)4491Jmr/J 017530 STOCK Iis2tm2(ACTB-tdTomato,-EGFP)Luo Trp53tm1Tyj Nf1tm1Par/J 012620 STOCK Trp53tm1Brd Brca1tm1Aash Tg(LGB-cre)74Acl/J 003262 STOCK Tg(Trp53A135V)L3Ber/JView Strains carrying other alleles of Trp53 (27 strains)
View Related Disease (OMIM) TermsRelated Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.Adrenocortical Carcinoma, Hereditary; ADCC (TP53)
Basal Cell Carcinoma, Susceptibility to, 7; BCC7 (TP53)
Breast Cancer (TP53)
Colorectal Cancer; CRC (TP53)
Glioma Susceptibility 1; GLM1 (TP53)
Hepatocellular Carcinoma (TP53)
Li-Fraumeni Syndrome 1; LFS1 (TP53)
Nasopharyngeal Carcinoma (TP53)
Osteogenic Sarcoma (TP53)
Pancreatic Cancer (TP53)
Papilloma of Choroid Plexus; CPP (TP53)
View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
Trp53tm4Att/Trp53tm4Attinvolves: 129S4/SvJae (conditional)
- cellular phenotype
- decreased cellular sensitivity to gamma-irradiation
- cell cycle is not arrested by gamma irradiation after treatment with adenovirus-cre (MGI Ref ID J:173395)
The following phenotype relates to a compound genotype created using this strain.
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Trp53tm4Att/Trp53tm4Att Gt(ROSA)26Sortm1(cre/ERT2)Tyj/?involves: 129S4/SvJae (conditional)
- cellular phenotype
- decreased apoptosis
- no apoptosis in mice treated with tamoxifen when measured 6 hours after radiation treatment (MGI Ref ID J:173395)
|Allele Name||targeted mutation 4, Laura D Attardi|
|Allele Type||Targeted (Floxed/Frt)|
|Strain of Origin||129S4/SvJae|
|Gene Symbol and Name||Trp53, transformation related protein 53|
|Gene Common Name(s)||BCC7; LFS1; P53; p44;|
|Molecular Note||A floxed puromycin/transcription stop cassette was inserted upstream of exon 2. In addition,mutations were inserted in exon 2 altering the codons for amino acid 25 from leucine to glutamine and amino acid 26 from tryptophan to serine. Further changes in exon 4 altered codon 53 from phenylalanine to glutamine and codon 54 from phenylalanine to serine. Both transactivation domains are incapacitated once the stop sequences are removed by cre expression. [MGI Ref ID J:173395]|
Brady CA; Jiang D; Mello SS; Johnson TM; Jarvis LA; Kozak MM; Kenzelmann Broz D; Basak S; Park EJ; McLaughlin ME; Karnezis AN; Attardi LD. 2011. Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression. Cell 145(4):571-83. [PubMed: 21565614] [MGI Ref ID J:173395]
Breeding & Husbandry When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes exhibit decreased fertility.
This strain is currently Under Development for Cryo.
|Wild-type from the colony|
|Considerations for Choosing Controls|
|Control Pricing Information for Genetically Engineered Mutant Strains.|
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