Lipid composition of whole brain and cerebellum in Hurler syndrome (MPS IH) mice.
Hurler syndrome (MPS IH) is caused by a mutation in the gene encoding alpha-L-iduronidase (IDUA) and leads to the accumulation of partially degraded glycosaminoglycans (GAGs). Ganglioside content is known to increase secondary to GAG accumulation. Most studies in organisms with MPS IH have focused on changes in gangliosides GM3 and GM2, without the study of other lipids. We evaluated the total lipid distribution in the whole brain and cerebellum of MPS IH (Idua⁻/⁻) and control (Idua(+/?)) mice at 6 months and at 12 months of age. The content of total sialic acid and levels of gangliosides GM3, GM2, and GD3 were greater in the whole brains of Idua⁻/⁻ mice then in Idua (+/?) mice at 12 months of age. No other significant lipid differences were found in either whole brain or in cerebellum at either age. The accumulation of ganglioside GD3 suggests that neurodegeneration occurs in the Idua⁻/⁻) mouse brain, but not to the extent seen in human MPS IH brain.
Department of Biology, Boston College, 140 Commonwealth Ave, Chestnut Hill, Boston, MA 02467, USA.
Karie A
KA
Heinecke
Brandon N
BN
Peacock
Bruce R
BR
Blazar
Jakub
J
Tolar
Thomas N
TN
Seyfried
D000818:Animals; D001923:Brain Chemistry; D002531:Cerebellum / Q000737:chemistry*; D004195:Disease Models, Animal; D005260:Female; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007068:Iduronidase / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008059:Mucopolysaccharidosis I / Q000235:genetics / Q000503:physiopathology*
D005732:Gangliosides; D006025:Glycosaminoglycans; D008055:Lipids; D007068:Iduronidase
J Med Genet. 1973 Jun;10(2):144-53
4268390
Indian J Med Res. 1969 Sep;57(9):1761-6
4244207
Tohoku J Exp Med. 1982 Jul;137(3):253-60
6810503
Ann Neurol. 2006 Aug;60(2):204-13
16718701
J Neurochem. 1982 Feb;38(2):551-9
7108555
Pediatr Neurol. 1991 May-Jun;7(3):186-90
1878098
J Neurochem. 2010 Nov;115(3):748-58
20731757
Genet Med. 2003 Jul-Aug;5(4):286-94
12865757
J Neurochem. 1975 Sep;25(3):229-32
1159420
Am J Pathol. 1984 Mar;114(3):487-95
6320652
Brain Res. 1986 May 28;374(2):260-9
2424561
Proc R Soc Med. 1936 Dec;30(2):158-60
19990935
Am J Dis Child. 1966 Dec;112(6):518-30
4224657
Adv Exp Med Biol. 1984;174:169-81
6741729
J Neurochem. 1978 May;30(5):965-73
96217
J Lipid Res. 1966 May;7(3):337-40
4959256
J Neurosci Res. 1990 May;26(1):105-11
2359143
Pathol Eur. 1968;3(2):431-9
4972156
Mol Genet Metab. 2005 Jan;84(1):18-24
15639191
Mol Cell Biochem. 1985 Sep;68(1):3-10
3903474
J Comp Neurol. 2004 Dec 20;480(4):415-26
15558784
Biochim Biophys Acta. 1957 Jun;24(3):604-11
13436486
J Biol Chem. 1957 May;226(1):497-509
13428781
Hum Gene Ther. 2002 Oct 10;13(15):1809-20
12396614
Brain Res Bull. 2007 Nov 1;74(6):429-38
17920451
J Neurochem. 1990 May;54(5):1598-607
2109043
Clin Orthop Relat Res. 1976 Jan-Feb;(114):116-33
131015
Bone Marrow Transplant. 2008 May;41(10):905-6
18278074
Arch Dis Child. 1967 Feb;42(221):62-9
4225314
Clin Genet. 1998 May;53(5):349-61
9660052
Biochim Biophys Acta. 1989 Sep 25;1005(2):109-17
2775765
J Neurochem. 1978 Jul;31(1):21-7
671019
Clin Pediatr (Phila). 1965 Aug;4:468-80
14333632
J Biol Chem. 1994 Dec 23;269(51):32418-25
7528216
Neurochem Int. 2008 May;52(6):1125-33
18207611
Proc Natl Acad Sci U S A. 1983 Oct;80(19):6091-5
6412235
Mol Genet Metab. 2007 Feb;90(2):171-80
17011223
J Neurochem. 1980 Jun;34(6):1399-411
6770045
J Neurochem. 1984 Oct;43(4):1152-62
6470710
Mol Genet Metab. 2001 Mar;72(3):199-208
11243725
J Neurol Sci. 1991 Jul;104(1):1-8
1919594
Mol Ther. 2004 Jun;9(6):866-75
15194053
Mol Genet Metab. 2007 Jul;91(3):239-50
17482862
Pediatr Res. 1979 Nov;13(11):1294-7
117422
Anal Biochem. 1978 Sep;89(2):437-50
103458
J Neuropathol Exp Neurol. 1965 Apr;24:341-51
14292252
Blood. 2010 Dec 9;116(24):5130-9
20847202
Mol Neurobiol. 2005 Aug;32(1):89-103
16077186
Biochem Genet. 2004 Aug;42(7-8):241-57
15487588
N Engl J Med. 1969 Aug 14;281(7):338-43
4240150
J Neurochem. 2004 May;89(3):645-53
15086521
Acta Paediatr Scand. 1969 May;58(3):220-8
4239322
AMA Arch Pathol. 1955 Sep;60(3):308-18
13248343
Brain Res. 1981 May 4;211(2):341-54
7016256
J Neurochem. 2001 Jan;76(1):77-86
11145980
Hum Mol Genet. 1997 Apr;6(4):503-11
9097952
Proc Natl Acad Sci U S A. 1972 Aug;69(8):2048-51
4262258
J Neurochem. 1985 Oct;45(4):1213-7
3928817
J Lipid Res. 1983 Sep;24(9):1243-50
6631248
FASEB J. 2001 Aug;15(10):1858-60
11481254
AJNR Am J Neuroradiol. 1993 Nov-Dec;14(6):1285-92
8279321
Glycobiology. 2010 Jan;20(1):78-86
19776077
Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19958-63
19903883
J Neurochem. 1979 Feb;32(2):293-300
762546
J Neurochem. 1966 Nov;13(11):1249-56
4958915
Ann Neurol. 2004 Jul;56(1):68-76
15236403
Scand J Clin Lab Invest. 1952;4(1):43-6
14921802
J Neurochem. 1983 Aug;41(2):491-505
6875549
Neurobiol Dis. 2007 Sep;27(3):265-77
17600724