2026-04-13T13:17:20Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1072672025-11-19T19:00:58Zcom_2072_1057col_2072_478777col_2072_478917
RECERCAT author Gómez Grau, Marta author Albaigès, Júlia author Casas, Josefina author Auladell i Costa, M. Carme author Dierssen, Mara author Vilageliu i Arqués, Lluïsa author Grinberg Vaisman, Daniel Raúl 2017-02-22T15:43:27Z2017-02-22T15:43:27Z2017-02-072017-02-22T15:43:27Z Niemann-Pick disease type C (NPC) is a rare neurovisceral disease caused mainly by mutations in the NPC1 gene. This autosomal recessive lysosomal disorder is characterised by the defective lysosomal secretion of cholesterol and sphingolipids. No effective therapy exists for the disease. We previously described a deep intronic point mutation (c.1554-1009G>A) in NPC1 that generated a pseudoexon, which could be corrected at the cellular level using antisense oligonucleotides. Here, we describe the generation of two mouse models bearing this mutation, one in homozygosity and the other in compound heterozygosity with the c.1920delG mutation. Both the homozygotes for the c.1554- 1009G>A mutation and the compound heterozygotes recapitulated the hallmarks of NPC. Lipid analysis revealed accumulation of cholesterol in the liver and sphingolipids in the brain, with both types of transgenic mice displaying tremor and ataxia at 7-8 weeks of age. Behavioural tests showed motor impairment, hyperactivity, reduced anxiety-like behaviour and impaired learning and memory performances, features consistent with those reported previously in NPC animal models and human patients. These mutant mice, the first NPC models bearing a pseudoexon-generating mutation, could be suitable for assessing the efficacy of specific splicing-targeted therapeutic strategies against NPC. cc-by (c) Gómez et al., 2017 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess Malalties de les glàndules endocrines Lisosomes Malalties rares Endocrine diseases Lysosomes Rare diseases New murine Niemann-Pick type C models bearing a pseudoexongenerating mutation recapitulate the main neurobehavioural and molecular features of the disease info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion