Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA173084 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The peptidase ClpP is conserved from bacteria to human. In the mitochondrial matrix, it multimerizes and forms a macromolecular proteasome-like cylinder. Because of its known relevance for the mitochondrial unfolded protein response during cell stress, we characterized two ClpP knock-out mouse founder lines and documented similar phenotypes. Ubiquitously, ClpP absence led to accumulation of its interactor protein ClpX without transcript upregulation. Interestingly, most wild-type tissues with substantial ClpP amounts had no detectable ClpX. This inverse correlation suggests that ClpX levels and degradation are regulated by ClpP. The expectation of similar protein levels, in view of a reported association of heptameric ClpP rings with hexameric ClpX rings, was confirmed only in testis of wild-type animals. Germline tissue was exceptional also in its vulnerability to ClpP deletion, with both founder lines showing complete infertility for males and females. Otherwise, ubiquitous mitochondrial dysfunction was apparent from severe growth retardation and reduced spontaneous motor activity of the animals, and from a pronounced decrease in pre-/postnatal survival. Spermatogenesis was found aborted at the spermatid stage, acrosomes and axonemes were not formed. Overall, tissue-specific roles of ClpP were evident by this massive effect for germ cells, mild bioenergetic deficits in muscle and liver tissues, and excellent compensation in brain. ClpX was previously reported to chaperone unfolded proteins and also DNA condensation in mitochondria, so it is likely that this pathway is particularly susceptible in germ cells. In conclusion, our study indicates that the role of ClpP in quality control is indispensable during development for cells with rapid changes of mitochondrial numbers, and is relevant during aging for growth and survival of the organism. Factorial design comparing ClpP knock-out mice with wild type littermates in five different tissues (brain, testis, liver, skeletal and heart muscle)
2013-07-17 | E-GEOD-40207 | biostudies-arrayexpress
Project description:Expression data from Adam10 knock out mice and wild type
| PRJNA134615 | ENA
Project description:Expression data from Gdap1 knock-out (deletion of exon 5) mice
| PRJNA224198 | ENA
Project description:Expression data from testis of day-7 Sohlh1 knock-out mice
| PRJNA125951 | ENA
Project description:The aim of the study was to investigate whether the trefoil peptide genes, in concerted action with a miRNA regulatory network, were contributing to nutritional maintrenance. Using a Tff2 knock-out mouse model, 48 specific miRNAs were noted to be significantly deregulated when compared to the wild type strain.
2012-01-01 | GSE25815 | GEO
Project description:The aim of the study was to investigate whether the trefoil peptide genes, in concerted action with a miRNA regulatory network, were contributing to nutritional maintrenance. Using a Tff3 knock-out mouse model, 21 specific miRNAs were noted to be significantly deregulated when compared to the wild type strain.
2010-09-20 | GSE23819 | GEO
Project description:Expression data of MCK conditional frataxin knock-out mice
| PRJNA145983 | ENA
Project description:Targeting the mitochondrial caseinolytic protease P (ClpP) is a potential novel strategy for treating leukemia. However, little is known about the therapeutic effects of ClpP in solid tumors. In this study, we identify a strong activator of the mitochondrial ClpP for subsequent use in targeted pancreatic ductal adenocarcinoma (PDAC) therapy. Analysis of clinical data demonstrated a positive association between ClpP expression and prognosis in PDAC patients. We validated that aberrant ClpP activation can lead to growth arrest in PDAC cells and tumors. We then performed high-throughput screening and synthetic optimization to develop a potent ClpP activator, ZG111, which promoted ClpP to degrade respiratory chain complexes and occurred in a ClpP-dependent manner. This resulted in impaired oxidative phosphorylation in the mitochondria and activation of JNK/c-Jun pathway and endoplasmic reticulum stress response. ZG111 also produced significant antitumor effects on tumors in cell-derived and patient-derived xenografted mice models. Altogether, our identification of ZG111 demonstrated that the aberrant activation of ClpP hydrolysis can be used as a potential therapeutic strategy to treat PDAC cancer.
2021-10-21 | GSE186091 | GEO
Project description:Expression data from Adam17 knock out mice and wild type
| PRJNA125859 | ENA
Project description:Differential proteolytic processing in control and mitochondrial clpp protease-deficient mice were compared.
2020-06-01 | PXD014159 | Pride