e.g., PRJCA000229; PRJNA784038; human
Accession PRJCA030156
Title Deficiency in LGMDR1 causative gene capn3b in zebrafish activates innate immunity and alters injury-induced leukocyte behavior
Relevance Model organism
Data types Raw sequence reads
Organisms Danio rerio
Description Mutations in calcium-dependent papain-like protease CALPAIN3 (CAPN3) cause Limb-Girdle Muscular Dystrophy Recessive Type 1 (LGMDR1), the most common limb-girdle muscular dystrophy in human. In addition to progressive muscle weakness in LGMDR1 patients, persistent inflammatory infiltration has been reported, yet the underlying mechanism remains elusive, especially when considering the newly defined role of CAPN3/Capn3b in the nucleolus. Here we report that loss-of-function of the zebrafish capn3b, the human CAPN3 counterpart, induces innate immunity akin to LGMDR1 patients. The capn3b mutant larvae were more susceptible to Listeria monocytogenes injection by recruiting more macrophages. Under the germ-free condition, transcriptome analysis of the capn3b mutant muscle revealed a significant upregulation of the chemokine production related genes. Consequently, more neutrophils were recruited to the injury site imposed by either muscle stabbing or tail fin amputation. Mechanism-wise, through nucleolar proteomics analysis, we find that NKAP, a factor related to activating the NF-κB function, is a target of CAPN3. We propose that the accumulation of Nkap and other factors in the capn3b mutant might be responsible, at least partly, for the activation of innate immunity. Our research demonstrates that the zebrafish capn3b mutant is a suitable model for studying the immunity-related progression of human LGMDR1.
Sample scope Multiisolate
Release date 2024-09-17
Grants
Agency program Grant ID Grant title
National Natural Science Foundation of China (NSFC) U21A20198
National Natural Science Foundation of China (NSFC) 32100658
Submitter Yayue Chen (yayuechen@zju.edu.cn)
Organization Zhejiang University
Submission date 2024-09-13

Project Data

Resource name Description
BioSample (32)  show -
GSA (1) -
CRA019013 Deficiency in LGMDR1 causative gene capn3b in zebrafish activates innate immunity and alters injury-induced leukocyte behavior