Journal article
Neurological Dysfunction in Early Maturity of a Model for Niemann–Pick C1 Carrier Status
YH Hung, M Walterfang, L Churilov, L Bray, LH Jacobson, KJ Barnham, NC Jones, TJ O’Brien, D Velakoulis, AI Bush
Neurotherapeutics | SPRINGER | Published : 2016
Abstract
Autosomal recessive inheritance of NPC1 with loss-of-function mutations underlies Niemann–Pick disease, type C1 (NP-C1), a lysosomal storage disorder with progressive neurodegeneration. It is uncertain from limited biochemical studies and patient case reports whether NPC1 haploinsufficiency can cause a partial NP-C1 phenotype in carriers. In the present study, we examined this possibility in heterozygotes of a natural loss-of-function mutant Npc1 mouse model. We found partial motor dysfunction and increased anxiety-like behavior in Npc1+/– mice by 9 weeks of age. Relative to Npc1+/+ mice, Npc1+/– mice failed to show neurodevelopmental improvements in motor coordination and balance on an acce..
View full abstractRelated Projects (1)
Grants
Awarded by Addi and Cassi Fund
Funding Acknowledgements
We thank Dr Steven Walkley for kindly providing us with the breeding pairs of heterozygous BALB/cJ Npc1<SUP>nih</SUP> mice. This work was supported, in part, by a research grant from the University of Pennsylvania Orphan Disease Center, and by grants from the Australian Niemann-Pick Type C Disease Foundation to Y.H.H., A.I.B., and M.W.; the Addi and Cassi Fund to Y.H.H. and A.I.B.; the National Health and Medical Research Council of Australia (AF79) to A.I.B.; and Cooperative Research Centre for Mental Health to A.I.B. The Florey Institute of Neuroscience and Mental Health acknowledges the strong support of the Victorian Government and, in particular, the funding from the Operational Infrastructure Support Grant.