Selected publications

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.

Sci Rep. 2019 Jan 28;9(1):799. doi: 10.1038/s41598-018-37235-w.

Majchrzak M1, Drela K1, Andrzejewska A1, Rogujski P1, Figurska S2, Fiedorowicz M3, Walczak P4,5, Janowski M1,4, Lukomska B1, Stanaszek L6.

Author information

1        NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

2        Laboratory for Genetically Modified Animals, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

3        Department of Experimental Pharmacology and Small Animal Magnetic Resonance Imaging Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

4        Johns Hopkins University School of Medicine, Institute for Cell Engineering, Division of MR Research, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD, USA.

5        Department of Neurosurgery, School of Medicine, Collegium Medicum, University of Warmia and Mazury, Olsztyn, 10-719, Poland.

6        NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. This email address is being protected from spambots. You need JavaScript enabled to view it..

Abstract

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.