Grainyhead-like 2 influences renal cyst growth in a mouse model
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA864781 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20730957_1.fastq.gz | Fastqsanger.gz | |||
| SRR20730957_2.fastq.gz | Fastqsanger.gz | |||
| SRR20730958_1.fastq.gz | Fastqsanger.gz | |||
| SRR20730958_2.fastq.gz | Fastqsanger.gz | |||
| SRR20730959_1.fastq.gz | Fastqsanger.gz |
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PKD2, encoding polycystin-1 (PC1) and polycystin-2 (PC2), which are required for the regula1on
of the renal tubular diameter. Loss of polycystin func1on results in cyst forma1on. Atypical forms
of ADPKD are caused by mutations in genes encoding endoplasmic reticulum (ER)-resident
proteins through mechanisms that are not well understood. Here, we investigate the func1on of
DNAJB11, an ER co-chaperone associated with atypical ADPKD. We generated mouse models with
constitutive and conditional Dnajb11 inactivation and Dnajb11-deficient renal epithelial cells to
investigate the mechanism underlying autosomal dominant inheritance, the specific cell types
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mirroring human disease characteristics. In contrast to classical ADPKD, cysts predominantly
originate from proximal tubules. Cyst formation begins in utero and the timing of Dnajb11
inactivation strongly influences disease severity. Furthermore, we identify impaired PC1 cleavage as a potential mechanism underlying DNAJB11-dependent cyst formation. Proteomic analysis of Dnajb11- and Pkd1-deficient cells reveals common and distinct pathways and dysregulated proteins, providing a foundation to better understand phenotypic differences between different forms of ADPKD.
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