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Deletion of the Mitochondrial Membrane Protein Fam210b Is Associated with the Development of Systemic Lupus Erythematosus.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Jul 01; Vol. 25 (13). Date of Electronic Publication: 2024 Jul 01. - Publication Year :
- 2024
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Abstract
- Mitochondrial dysfunction has been increasingly recognized as a trigger for systemic lupus erythematosus (SLE). Recent bioinformatics studies have suggested Fam210b as a significant candidate for the classification and therapeutic targeting of SLE. To experimentally prove the role of Fam210b in SLE, we constructed Fam210b knockout ( Fam210b <superscript>-/-</superscript> ) mice using the CRISPR-Cas9 method. We found that approximately 15.68% of Fam210b <superscript>-/-</superscript> mice spontaneously developed lupus-like autoimmunity, which was characterized by skin ulcerations, splenomegaly, and an increase in anti-double-stranded DNA (anti-dsDNA) IgG antibodies and anti-nuclear antibodies(ANA). Single-cell sequencing showed that Fam210b was mainly expressed in erythroid cells. Critically, the knockout of Fam210b resulted in abnormal erythrocyte differentiation and development in the spleens of mice. Concurrently, the spleens exhibited an increased number of CD71 <superscript>+</superscript> erythroid cells, along with elevated levels of reactive oxygen species (ROS) in the erythrocytes. The co-culture of CD71 <superscript>+</superscript> erythroid cells and lymphocytes resulted in lymphocyte activation and promoted dsDNA and IgG production. In summary, Fam210b knockout leads to a low probability of lupus-like symptoms in mice through the overproduction of ROS in CD71 <superscript>+</superscript> erythroid cells. Thus, Fam210b reduction may serve as a novel key marker that triggers the development of SLE.
- Subjects :
- Animals
Mice
Mitochondrial Proteins genetics
Mitochondrial Proteins metabolism
Reactive Oxygen Species metabolism
Antibodies, Antinuclear
Mitochondrial Membranes metabolism
Erythroid Cells metabolism
Erythroid Cells pathology
Disease Models, Animal
Immunoglobulin G metabolism
Mice, Inbred C57BL
Spleen metabolism
Spleen pathology
Membrane Proteins genetics
Membrane Proteins metabolism
Female
Lupus Erythematosus, Systemic genetics
Lupus Erythematosus, Systemic metabolism
Lupus Erythematosus, Systemic pathology
Mice, Knockout
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39000360
- Full Text :
- https://doi.org/10.3390/ijms25137253