PMID- 10021458
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 103
IP  - 4
DP  - 1999 Feb
TI  - A genetic model of substrate deprivation therapy for a glycosphingolipid storage 
      disorder.
PG  - 497-505
AB  - Inherited defects in the degradation of glycosphingolipids (GSLs) cause a group
      of severe diseases known as GSL storage disorders. There are currently no
      effective treatments for the majority of these disorders. We have explored a new 
      treatment paradigm, substrate deprivation therapy, by constructing a genetic
      model in mice. Sandhoff's disease mice, which abnormally accumulate GSLs, were
      bred with mice that were blocked in their synthesis of GSLs. The mice with
      simultaneous defects in GSL synthesis and degradation no longer accumulated GSLs,
      had improved neurologic function, and had a much longer life span. However, these
      mice eventually developed a late-onset neurologic disease because of accumulation
      of another class of substrate, oligosaccharides. The results support the validity
      of the substrate deprivation therapy and also highlight some limitations.
FAU - Liu, Y
AU  - Liu Y
AD  - Genetics of Development and Disease Branch, National Institute of Diabetes and
      Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 
      20892, USA.
FAU - Wada, R
AU  - Wada R
FAU - Kawai, H
AU  - Kawai H
FAU - Sango, K
AU  - Sango K
FAU - Deng, C
AU  - Deng C
FAU - Tai, T
AU  - Tai T
FAU - McDonald, M P
AU  - McDonald MP
FAU - Araujo, K
AU  - Araujo K
FAU - Crawley, J N
AU  - Crawley JN
FAU - Bierfreund, U
AU  - Bierfreund U
FAU - Sandhoff, K
AU  - Sandhoff K
FAU - Suzuki, K
AU  - Suzuki K
FAU - Proia, R L
AU  - Proia RL
LA  - eng
GR  - P30 HD003110/HD/NICHD NIH HHS/United States
GR  - R01 NS024453/NS/NINDS NIH HHS/United States
GR  - P30-HD 03110/HD/NICHD NIH HHS/United States
GR  - R01-NS 24453/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Glycolipids)
RN  - 0 (Glycosphingolipids)
RN  - 0 (Oligosaccharides)
RN  - EC 2.4.1.- (N-Acetylgalactosaminyltransferases)
RN  - EC 2.4.1.41 (polypeptide N-acetylgalactosaminyltransferase)
RN  - EC 2.4.1.92 ((N-acetylneuraminyl)-galactosylglucosylceramide
      N-acetylgalactosaminyltransferase)
RN  - EC 3.2.1.52 (beta-N-Acetylhexosaminidases)
SB  - AIM
SB  - IM
CIN - J Clin Invest. 1999 Feb;103(4):439-40. PMID: 10021449
MH  - Animals
MH  - Behavior, Animal
MH  - Disease Models, Animal
MH  - Female
MH  - Glycolipids/metabolism
MH  - Glycosphingolipids/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - *Models, Genetic
MH  - N-Acetylgalactosaminyltransferases/genetics/*physiology
MH  - Oligosaccharides/metabolism
MH  - Research Design
MH  - Sandhoff Disease/genetics/metabolism/*therapy
MH  - Substrate Specificity
MH  - beta-N-Acetylhexosaminidases/genetics/*physiology
PMC - PMC408106
EDAT- 1999/02/18 00:00
MHDA- 1999/02/18 00:01
CRDT- 1999/02/18 00:00
PHST- 1999/02/18 00:00 [pubmed]
PHST- 1999/02/18 00:01 [medline]
PHST- 1999/02/18 00:00 [entrez]
AID - 10.1172/JCI5542 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Feb;103(4):497-505. doi: 10.1172/JCI5542.