Peer-reviewedCC BY 4.0International Journal of Molecular Sciences
Loss of Sidt2 in Mice Resembles Danon Disease and Results in Induction of a Type I Interferon Response with Increased Apoptosis
10 affiliations
- 1The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3050, Australia
- 2Department of Medical Biology, University of Melbourne, Parkville, VIC 3050, Australia
- 3Murdoch Children’s Research Institute, Parkville, VIC 3052, Australia
- 4Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia
- 5Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
- 6Department of Pathology, Boston Children’s Hospital, Boston, MA 02115, USA
- 7Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- 8Department of Surgery, Division of Cardiovascular Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- 9Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
- 10Royal Children’s Hospital, Parkville, VIC 3052, Australia
Abstract
SIDT2 is a lysosomal membrane protein that—together with LAMP2—has been implicated in a recently described process known as RNAutophagy. Mutations in LAMP2 have long been known to cause Danon disease, a rare lysosomal storage disorder that affects multiple organ systems including brain and skeletal muscle. Recently, we have shown that loss of SIDT2 function in both humans and mice causes brain dysfunction, and it has been previously observed that loss of SIDT2 in mice also leads to muscle damage and reduced muscle strength. Here, we show that changes in the skeletal muscle of Sidt2−/− mice are reminiscent of those seen in Danon disease as evidenced by accumulation of autophagic vacuoles with sarcolemmal features, selective atrophy of fast twitch fibers, and a shared alteration in gene expression. Moreover, we find that loss of SIDT2 not only leads to impaired autophagy in skeletal muscle as previously described but also stimulates a type I interferon response and increased apoptosis.
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BibTeX
@article{barrios2026loss,
title = {{Loss of Sidt2 in Mice Resembles Danon Disease and Results in Induction of a Type I Interferon Response with Increased Apoptosis}},
author = {Marilou H. Barrios and Tan A. Nguyen and Peter J. Houweling and Daniel Frank and Fleur C. Garton and Hart G. Lidov and Ellen Tsui and Alexandra L. Garnham and Amrut V. Ambardekar and Gordon K. Smyth and Luisa Mestroni and Joseph C. Cleveland and Matthew R. G. Taylor and Kathryn N. North and Craig P. Hunter and Ken C. Pang},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209158},
url = {https://www.mdpi.com/1422-0067/27/20/9158},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Loss of Sidt2 in Mice Resembles Danon Disease and Results in Induction of a Type I Interferon Response with Increased Apoptosis
AU - Marilou H. Barrios
AU - Tan A. Nguyen
AU - Peter J. Houweling
AU - Daniel Frank
AU - Fleur C. Garton
AU - Hart G. Lidov
AU - Ellen Tsui
AU - Alexandra L. Garnham
AU - Amrut V. Ambardekar
AU - Gordon K. Smyth
AU - Luisa Mestroni
AU - Joseph C. Cleveland
AU - Matthew R. G. Taylor
AU - Kathryn N. North
AU - Craig P. Hunter
AU - Ken C. Pang
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209158
UR - https://www.mdpi.com/1422-0067/27/20/9158
AB - SIDT2 is a lysosomal membrane protein that—together with LAMP2—has been implicated in a recently described process known as RNAutophagy. Mutations in LAMP2 have long been known to cause Danon disease, a rare lysosomal storage disorder that affects multiple organ systems including brain and skeletal muscle. Recently, we have shown that loss of SIDT2 function in both humans and mice causes brain dysfunction, and it has been previously observed that loss of SIDT2 in mice also leads to muscle damage and reduced muscle strength. Here, we show that changes in the skeletal muscle of Sidt2−/− mice are reminiscent of those seen in Danon disease as evidenced by accumulation of autophagic vacuoles with sarcolemmal features, selective atrophy of fast twitch fibers, and a shared alteration in gene expression. Moreover, we find that loss of SIDT2 not only leads to impaired autophagy in skeletal muscle as previously described but also stimulates a type I interferon response and increased apoptosis.
SN - 1422-0067
ER -