An immune deficient mouse model for mucopolysaccharidosis IIIA (Sanfilippo syndrome).

Autor: Pollock K; Stem Cell Program and Institute for Regenerative Cures, University of California Davis Health System, Sacramento, CA, USA. kmpollock@ucdavis.edu., Noritake S; Stem Cell Program and Institute for Regenerative Cures, University of California Davis Health System, Sacramento, CA, USA., Imai DM; Comparative Pathology Laboratory, University of California Davis, School of Veterinary Medicine, Davis, CA, USA., Pastenkos G; Comparative Pathology Laboratory, University of California Davis, School of Veterinary Medicine, Davis, CA, USA., Olson M; Stem Cell Program and Institute for Regenerative Cures, University of California Davis Health System, Sacramento, CA, USA., Cary W; Stem Cell Program and Institute for Regenerative Cures, University of California Davis Health System, Sacramento, CA, USA., Yang S; Stem Cell Program and Institute for Regenerative Cures, University of California Davis Health System, Sacramento, CA, USA., Fierro FA; Stem Cell Program and Institute for Regenerative Cures, University of California Davis Health System, Sacramento, CA, USA., White J; Stem Cell Program and Institute for Regenerative Cures, University of California Davis Health System, Sacramento, CA, USA., Graham J; Stem Cell Program and Institute for Regenerative Cures, University of California Davis Health System, Sacramento, CA, USA., Dahlenburg H; Stem Cell Program and Institute for Regenerative Cures, University of California Davis Health System, Sacramento, CA, USA., Johe K; ReMotor Therapeutics, Inc., San Diego, CA, USA., Nolta JA; Stem Cell Program and Institute for Regenerative Cures, University of California Davis Health System, Sacramento, CA, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Oct 27; Vol. 13 (1), pp. 18439. Date of Electronic Publication: 2023 Oct 27.
DOI: 10.1038/s41598-023-45178-0
Abstrakt: Mucopolysaccharidosis III (MPSIII, Sanfilippo syndrome) is a devastating lysosomal storage disease that primarily affects the central nervous system. MPSIIIA is caused by loss-of-function mutations in the gene coding for sulfamidase (N-sulfoglucosamine sulfohydrolase/SGSH) resulting in SGSH enzyme deficiency, a buildup of heparin sulfate and subsequent neurodegeneration. There is currently no cure or disease modifying treatment for MPSIIIA. A mouse model for MPSIIIA was characterized in 1999 and later backcrossed onto the C57BL/6 background. In the present study, a novel immune deficient MPSIIIA mouse model (MPSIIIA-TKO) was created by backcrossing the immune competent, C57BL/6 MPSIIIA mouse to an immune deficient mouse model lacking Rag2, CD47 and Il2rg genes. The resulting mouse model has undetectable SGSH activity, exhibits histological changes consistent with MPSIIIA and lacks T cells, B cells and NK cells. This new mouse model has the potential to be extremely useful in testing human cellular therapies in an animal model as it retains the MPSIIIA disease phenotype while tolerating xenotransplantation.
(© 2023. The Author(s).)
Databáze: MEDLINE
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