PMID- 34844863
OWN - NLM
STAT- MEDLINE
DCOM- 20220328
LR  - 20240303
IS  - 1096-7206 (Electronic)
IS  - 1096-7192 (Linking)
VI  - 134
IP  - 4
DP  - 2021 Dec
TI  - Neuropathology of murine Sanfilippo D syndrome.
PG  - 323-329
LID - S1096-7192(21)00828-3 [pii]
LID - 10.1016/j.ymgme.2021.11.010 [doi]
AB  - Sanfilippo D syndrome (mucopolysaccharidosis type IIID) is a lysosomal storage 
      disorder caused by the deficiency of N-acetylglucosamine-6-sulfatase (GNS). A 
      mouse model was generated by constitutive knockout of the Gns gene. We studied 
      affected mice and controls at 12, 24, 36, and 48 weeks of age for 
      neuropathological markers of disease in the somatosensory cortex, primary motor 
      cortex, ventral posterior nuclei of the thalamus, striatum, hippocampus, and 
      lateral and medial entorhinal cortex. We found significantly increased 
      immunostaining for glial fibrillary associated protein (GFAP), CD68 (a marker of 
      activated microglia), and lysosomal-associated membrane protein-1 (LAMP-1) in 
      Sanfilippo D mice compared to controls at 12 weeks of age in all brain regions. 
      Intergroup differences were marked for GFAP and CD68 staining, with levels in 
      Sanfilippo D mice consistently above controls at all age groups. Intergroup 
      differences in LAMP-1 staining were more pronounced in 12- and 24-week age groups 
      compared to 36- and 48-week groups, as control animals showed some LAMP-1 
      staining at later timepoints in some brain regions. We also evaluated the 
      somatosensory cortex, medial entorhinal cortex, reticular nucleus of the 
      thalamus, medial amygdala, and hippocampal hilus for subunit c of mitochondrial 
      ATP synthase (SCMAS). We found a progressive accumulation of SCMAS in most brain 
      regions of Sanfilippo D mice compared to controls by 24 weeks of age. Cataloging 
      the regional neuropathology of Sanfilippo D mice may aid in understanding the 
      disease pathogenesis and designing preclinical studies to test brain-directed 
      treatments.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Takahashi, Keigo
AU  - Takahashi K
AD  - Department of Pediatrics, Washington University in St. Louis, St. Louis, MO 
      63110, USA.
FAU - Le, Steven Q
AU  - Le SQ
AD  - Department of Pediatrics, Washington University in St. Louis, St. Louis, MO 
      63110, USA.
FAU - Kan, Shih-Hsin
AU  - Kan SH
AD  - Children's Hospital Orange County Research Institute, Orange, CA 92868, USA.
FAU - Jansen, Matthew J
AU  - Jansen MJ
AD  - Department of Pediatrics, Washington University in St. Louis, St. Louis, MO 
      63110, USA.
FAU - Dickson, Patricia I
AU  - Dickson PI
AD  - Department of Pediatrics, Washington University in St. Louis, St. Louis, MO 
      63110, USA. Electronic address: pdickson@wustl.edu.
FAU - Cooper, Jonathan D
AU  - Cooper JD
AD  - Department of Pediatrics, Washington University in St. Louis, St. Louis, MO 
      63110, USA.
LA  - eng
GR  - R01 NS088766/NS/NINDS NIH HHS/United States
GR  - R41 NS089061/NS/NINDS NIH HHS/United States
GR  - R42 NS089061/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20211124
PL  - United States
TA  - Mol Genet Metab
JT  - Molecular genetics and metabolism
JID - 9805456
RN  - 0 (Lamp1 protein, mouse)
RN  - 0 (Lysosomal Membrane Proteins)
RN  - EC 3.6.1.- (mitochondrial ATPase subunit c)
RN  - EC 3.6.3.- (Mitochondrial Proton-Translocating ATPases)
SB  - IM
MH  - Animals
MH  - Brain/*pathology
MH  - Female
MH  - Gliosis/etiology
MH  - Lysosomal Membrane Proteins/analysis
MH  - Male
MH  - Mice
MH  - Microglia/physiology
MH  - Mitochondrial Proton-Translocating ATPases/analysis
MH  - Mucopolysaccharidosis III/etiology/metabolism/*pathology
OTO - NOTNLM
OT  - Glycosaminoglycan
OT  - Lysosomal storage disease
OT  - Mucopolysaccharidosis
COIS- Declaration of Competing Interest Dr. Dickson receives research support from 
      Genzyme and M6P Therapeutics. Dr. Cooper receives research support from 
      Regenexbio and Neurogene.
EDAT- 2021/12/01 06:00
MHDA- 2022/03/29 06:00
CRDT- 2021/11/30 05:51
PHST- 2021/10/01 00:00 [received]
PHST- 2021/11/19 00:00 [revised]
PHST- 2021/11/20 00:00 [accepted]
PHST- 2021/12/01 06:00 [pubmed]
PHST- 2022/03/29 06:00 [medline]
PHST- 2021/11/30 05:51 [entrez]
AID - S1096-7192(21)00828-3 [pii]
AID - 10.1016/j.ymgme.2021.11.010 [doi]
PST - ppublish
SO  - Mol Genet Metab. 2021 Dec;134(4):323-329. doi: 10.1016/j.ymgme.2021.11.010. Epub 
      2021 Nov 24.