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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 01, 2021 |
| Title |
The common germline TP53-R337H mutation is hypomorphic and confers incomplete tumor penetrance and late tumor onset in a mouse model |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The TP53-R337H founder mutation exists at high frequency throughout southern Brazil and represents the most common germline TP53 mutation reported to date. It was originally identified in pediatric adrenocortical tumors in families with no reported history of cancer. The R337H mutation has since been found in association with early-onset breast cancers and Li-Fraumeni syndrome. To study this variability in tumor susceptibility we generated a knockin mutant p53 mouse model (R334H). Endogenous murine R334H is naturally expressed at abnormally high levels in multiple tissues and is functionally compromised in a cell type and stress-specific manner. The mutant p53 mice develop tumors with long latency and incomplete penetrance, consistent with many human carriers being at a low, but elevated risk for cancer
We used microarrays to compare the global programme of gene expression in thymocytes obtained from WT or TP53R337H/R337H mutant mice that had either received 5 Gy whole body irradiation or no irradiation.
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| Overall design |
The missense mutation TP53 R337H was introduced into murine 129 embryonic stem (ES) cells by site-directed mutagenesis. ES clones harboring the mutation were then injected into C57BL6/J blastocysts to achieve germline transmission of the TP53R337H mutant allele. Mice were back-crossed against C57BL6/J mice and heterozygous pups were mated to obtain TP53R337H/R337H offspring. WT or TP53R337H/R337H mutant mice were irradiated using 5 Gy whole body radiation, euthanized 6 hours post-irradiation and thymocytes harvested for RNA extraction. We used four mice per treatment group, except for the WT irradiated group where duplicate mice were used.
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| Contributor(s) |
Jeffers J, Pinto EM, Rehg J, Wang J, Neale G, Figueiredo BC, Rodriguez-Galindo C, Ribeiro RC, Zambetti GP |
| Citation(s) |
33637564 |
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| Submission date |
Feb 16, 2021 |
| Last update date |
Jun 01, 2021 |
| Contact name |
Geoffrey Neale |
| E-mail(s) |
geoffrey.neale@stjude.org
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| Organization name |
St Jude Childrens Research Hospital
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| Department |
Hartwell Center
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| Street address |
262 Danny Thomas Place
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| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (14)
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| GSM5086032 |
JRJ014: WT thymocytes non-irradiated, replicate 1 |
| GSM5086033 |
JRJ015: WT thymocytes non-irradiated, replicate 2 |
| GSM5086034 |
JRJ016: WT thymocytes non-irradiated, replicate 3 |
| GSM5086035 |
JRJ017: WT thymocytes non-irradiated, replicate 4 |
| GSM5086036 |
JRJ018: WT thymocytes irradiated, replicate 1 |
| GSM5086037 |
JRJ019: WT thymocytes irradiated, replicate 2 |
| GSM5086038 |
JRJ024: TP53 mutant thymocytes non-irradiated, replicate 1 |
| GSM5086039 |
JRJ025: TP53 mutant thymocytes non-irradiated, replicate 2 |
| GSM5086040 |
JRJ026: TP53 mutant thymocytes non-irradiated, replicate 3 |
| GSM5086041 |
JRJ027: TP53 mutant thymocytes non-irradiated, replicate 4 |
| GSM5086042 |
JRJ028: TP53 mutant thymocytes irradiated, replicate 1 |
| GSM5086043 |
JRJ030: TP53 mutant thymocytes irradiated, replicate 2 |
| GSM5086044 |
JRJ031: TP53 mutant thymocytes irradiated, replicate 3 |
| GSM5086045 |
JRJ032: TP53 mutant thymocytes irradiated, replicate 4 |
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| Relations |
| BioProject |
PRJNA702070 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE166819_RAW.tar |
123.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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