SOD1/Rag2 Mice with Low Copy Number of SOD1 Gene as a New Long-Living Immunodeficient Model of ALS

SOD1/Rag2 Mice with Low Copy Number of SOD1 Gene as a New Long-Living Immunodeficient Model of ALS

The most recent research concerning amyotrophic lateral sclerosis (ALS) emphasizes the role of glia in disease development. Thus, one can suspect that the effective therapeutic strategy in treatment of ALS would be replacement of defective glia. One of the basic problems with human glial progenitors...

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Bibliographic Details
Published in:Scientific reports Vol. 9; no. 1; p. 799
Main Authors: Majchrzak, M., Drela, K., Andrzejewska, A., Rogujski, P., Figurska, S., Fiedorowicz, M., Walczak, P., Janowski, M., Lukomska, B., Stanaszek, L.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 28-01-2019
Nature Publishing Group
Subjects:
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Amyotrophic lateral sclerosis
Copy number
Glial stem cells
Humanities and Social Sciences
Immunodeficiency
Life span
Magnetic resonance imaging
Motor nuclei
multidisciplinary
Mutants
RAG2 protein
Rodents
Science
Science (multidisciplinary)
Stem cell transplantation
Stem cells
Superoxide dismutase
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Summary:The most recent research concerning amyotrophic lateral sclerosis (ALS) emphasizes the role of glia in disease development. Thus, one can suspect that the effective therapeutic strategy in treatment of ALS would be replacement of defective glia. One of the basic problems with human glial progenitors (hGRPs) replacement strategies is the time needed for the cells to become fully functional in vivo . The lifespan of most popular high copy number SOD1 mutant mice might be too short to acknowledge benefits of transplanted cells. We focused on developing immunodeficient rag2 − / − model of ALS with lower number of transgene copies and longer lifespan. The obtained hSOD1/rag2 double mutant mice have been characterized. QPCR analysis revealed that copy number of hSOD1 transgene varied in our colony (4–8 copies). The difference in transgene copy number may be translated to significant impact on the lifespan. The death of long- and short-living hSOD1/rag2 mice is preceded by muscular weakness as early as one month before death. Importantly, based on magnetic resonance imaging we identified that mutant mice demonstrated abnormalities within the medullar motor nuclei. To conclude, we developed long-living double mutant hSOD1/rag2 mice, which could be a promising model for testing therapeutic utility of human stem cells.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-37235-w