title: Cystine accumulation in the CNS results in severe age-related memory deficits.
abstract: Cystinosis is a lysosomal storage disorder characterised by progressive cystine accumulation. The causative gene, CTNS, encodes cystinosin, the lysosomal cystine transporter. Neurological deterioration is one of the last symptoms to appear and the least well characterised. Visuospatial memory deficits have been documented in patients. To determine whether the cystinosis mouse model presents similar anomalies, we studied the learning and memory abilities of young and middle-aged Ctns(-/-) mice. We did not detect deficits in young Ctns(-/-) mice. In contrast, spatial reference and working memory deficits were detected in middle-aged Ctns(-/-) mice. Elevated cystine levels were detected in the hippocampus, cerebellum, forebrain and brainstem of all Ctns(-/-) mice, which increased with age and were consistent with the appearance of impairments. Our results strongly suggest that the cystinosis-associated CNS anomalies are due to progressive cystine accumulation. Furthermore, the Ctns(-/-) mice serve as a model to investigate the evolution of these anomalies and test the efficiency of existing and novel treatments to cross the blood-brain barrier and reduce lysosomal cystine levels.
authors.affiliation: Inserm U710, 34095 Montpellier, France.
authors.forename: Tangui
authors.initials: T
authors.lastname: Maurice
authors.forename: Claire
authors.initials: C
authors.lastname: Hippert
authors.forename: Nicolas
authors.initials: N
authors.lastname: Serratrice
authors.forename: Grégor
authors.initials: G
authors.lastname: Dubois
authors.forename: Chantal
authors.initials: C
authors.lastname: Jacquet
authors.forename: Corinne
authors.initials: C
authors.lastname: Antignac
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Kremer
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Kalatzis
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003553:Cystine / Q000378:metabolism*; D008568:Memory; D008569:Memory Disorders / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014018:Tissue Distribution
chemical_list: D003553:Cystine