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Series GSE248747 Query DataSets for GSE248747
Status Public on Nov 28, 2023
Title Combined absence of Trp53 target genes Zmat3, Puma and p21 cause a high incidence of cancer in mice
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Transcriptional activation of target genes is essential for TP53-mediated tumour suppression, though the roles of the diverse TP53-activated target genes in tumour suppression remains poorly understood. Knockdown of Zmat3, an RNA-binding zinc-finger protein involved in regulating alternative splicing, in haematopoietic cells by shRNA caused leukaemia only with the concomitant absence of the Puma and p21, the critical effectors of Trp53-mediated apoptosis and cell cycle arrest respectively. We were interested to further investigate the role of ZMAT3 in tumour suppression beyond the haematopoietic system. Therefore, we generated Zmat3 knockout and compound gene knockout mice, lacking Zmat3 and p21, Zmat3 and Puma or all three genes. Puma-/-p21-/-Zmat3-/- triple knockout mice developed tumours at a significantly higher frequency compared to wild-type, Puma-/-Zmat3-/- or p21-/-Zmat3-/-deficient mice. Interestingly, we observed that the triple knockout and Puma-/-Zmat3-/- double deficient animals succumbed to lymphoma, while p21-/-Zmat3-/- animals developed mainly solid cancers. This analysis suggests that in addition to ZMAT3 loss, additional TRP53-regulated processes must be disabled simultaneously for TRP53-mediated tumour suppression to fail. Our findings reveal that the absence of different TRP53 regulated tumour suppressive processes changes the tumour spectrum, indicating that different TRP53 tumour suppressive pathways are more critical in different tissues.
Overall design To investigate the impact of combined loss of Zmat3, Puma and p21 in Trp53-mediated tumour suppression we crossed Zmat3 -/- (ZKO) with Puma -/- p21 -/- mice to obtain Puma -/- p21 -/- Zmat3 -/- animals /TKOs).
Whole thymus from 8-12 week old mice were isolated and single cell suspension made by gentle mashing with a 70uL filter. 5 million cells were used for RNA extraction.
We then performed gene expression profiling using RNA-seq data
We were interested in the expression differences between Zmat3 KO mice and those with a triple KO (Zmat3, p21 & Puma). We also compared each of them to wild-type samples.
Contributor(s) Brennan MS, Brinkmann K, Sola GR, Healey G, Gibson L, Gangoda L, Potts M, Lieschke E, Wilcox S, Strasser A, Herold MJ, Janic A
Citation(s) 38110554
BioProject PRJNA1043715
Submission date Nov 27, 2023
Last update date Feb 15, 2024
Contact name Gerard Romero
Organization name Universitat Pompeu Fabra
Department Dpt of Medicine and Life Sciences, Universitat Pompeu Fabra (MELIS/UPF)
Street address Doctor Aiguader, 88
City Barcelona
State/province Catalonia
ZIP/Postal code 08003
Country Spain
Platforms (1)
GPL30172 NextSeq 2000 (Mus musculus)
Samples (11)
GSM7919398 Wild-type 1
GSM7919399 Wild-type 2
GSM7919400 Wild-type 3

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Supplementary file Size Download File type/resource
GSE248747_Raw_counts_matrix.txt.gz 617.7 Kb (ftp)(http) TXT
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