Npc1 deficiency in the C57BL/6J genetic background enhances Niemann–Pick disease type C spleen pathology

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dc.catalogadorgjm
dc.contributor.authorParra Cares, Julio Alejandro
dc.contributor.authorKlein, Andres D.
dc.contributor.authorCastro, Juan Francisco
dc.contributor.authorMorales France, María Gabriela
dc.contributor.authorMosqueira Montero, Matías José
dc.contributor.authorValencia Araya, Ilse
dc.contributor.authorCortés Mora, Víctor Antonio
dc.contributor.authorRigotti Rivera, Attilio
dc.contributor.authorZanlungo Matsuhiro, Silvana
dc.date.accessioned2023-05-19T20:50:40Z
dc.date.available2023-05-19T20:50:40Z
dc.date.issued2011
dc.description.abstractNiemann–Pick type C (NPC) disease is an autosomal recessive neurovisceral lipid storage disorder. The affected genes are NPC1 and NPC2. Mutations in either gene lead to intracellular cholesterol accumulation. There are three forms of the disease, which are categorized based on the onset and severity of the disease: the infantile form, in which the liver and spleen are severely affected, the juvenile form, in which the liver and brain are affected, and the adult form, which affects the brain. In mice, a spontaneous mutation in the Npc1 gene originated in the BALB/c inbred strain mimics the juvenile form of the disease. To study the influence of genetic background on the expression of NPC disease in mice, we transferred the Npc1 mutation from the BALB/c to C57BL/6J inbred background. We found that C57BL/6J-Npc1−/− mice present with a much more aggressive form of the disease, including a shorter lifespan than BALB/c-Npc1−/− mice. Surprisingly, there was no difference in the amount of cholesterol in the brains of Npc1−/− mice of either mouse strain. However, Npc1−/− mice with the C57BL/6J genetic background showed striking spleen damage with a marked buildup of cholesterol and phospholipids at an early age, which correlated with large foamy cell clusters. In addition, C57BL/6J Npc1−/− mice presented red cell abnormalities and abundant ghost erythrocytes that correlated with a lower hemoglobin concentration. We also found abnormalities in white cells, such as cytoplasmic granulation and neutrophil hypersegmentation that included lymphopenia and atypias. In conclusion, Npc1 deficiency in the C57BL6/J background is associated with spleen, erythrocyte, and immune system abnormalities that lead to a reduced lifespan.
dc.fechaingreso.objetodigital2023-07-14
dc.fuente.origenORCID
dc.identifier.doi10.1016/j.bbrc.2011.08.096
dc.identifier.eissn1090-2104
dc.identifier.issn0006-291X
dc.identifier.pubmedidPMID: 21910975
dc.identifier.urihttps://doi.org/10.1016/j.bbrc.2011.08.096
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/70310
dc.information.autorucEscuela de Medicina; Parra Cares, Julio Alejandro; S/I; 149076
dc.information.autorucFacultad de Ciencias Biológicas; Klein, Andres D., S/I; 2966
dc.information.autorucEscuela de Medicina; Castro, Juan Francisco; S/I; 8518
dc.information.autorucFacultad de Ciencias Biológicas; Morales France, María Gabriela; S/I; 4922
dc.information.autorucFacultad de Ciencias Biológicas; Mosqueira Montero, Matías José; S/I; 1231
dc.information.autorucEscuela de Medicina; Valencia Araya, Ilse; S/I; 8634
dc.information.autorucFacultad de Ciencias Biológicas; Cortés Mora, Víctor Antonio; 0000-0002-1658-0965; 7576
dc.information.autorucEscuela de Medicina; Rigotti Rivera, Attilio; 0000-0002-0495-3525; 68489
dc.information.autorucEscuela de Medicina; Zanlungo Matsuhiro, Silvana; 0000-0001-8383-9829; 72650
dc.issue.numero3
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final406
dc.pagina.inicio400
dc.revistaBiochemical and Biophysical Research Communications
dc.rightsacceso restringido
dc.subjectNiemann–Pick type C diseasees_ES
dc.subjectNPC1es_ES
dc.subjectCholesteroles_ES
dc.subjectLiveres_ES
dc.subjectSpleenes_ES
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.otherMedicina y saludes_ES
dc.titleNpc1 deficiency in the C57BL/6J genetic background enhances Niemann–Pick disease type C spleen pathologyes_ES
dc.typeartículo
dc.volumen413
sipa.codpersvinculados149076
sipa.codpersvinculados2966
sipa.codpersvinculados8518
sipa.codpersvinculados4922
sipa.codpersvinculados1231
sipa.codpersvinculados8634
sipa.codpersvinculados7576
sipa.codpersvinculados68489
sipa.codpersvinculados72650
sipa.indexPubmed
sipa.trazabilidadORCID;14-07-2023
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