RT Journal Article
T1 A murine model of BSCL2-associated Celia's encephalopathy
A1 Rabano, Alberto
A1 Burgueño-García, Iván
A1 Lampón-Fernández, Laura
A1 Díaz-López, Everardo Josué
A1 Prado-Moraña, Teresa
A1 San Millán, Beatriz
A1 Cobelo Gómez, Silvia
A1 Sánchez Iglesias, Sofía
A1 Senra, Ana
A1 Aguiar, Pablo
A1 Gómez Lado, Noemí
A1 García Varela, Lara
A1 Fernández-Pombo, Antía
A1 Araujo-Vilar, David
K1 BSCL2
K1 Seipin
K1 PELD
K1 Transgenic mouse
K1 Neurodegeneration
K1 Celia's encephalopathy
AB Celia's encephalopathy or progressive encephalopathy with/without lipodystrophy is a neurodegenerative disease with a fatal prognosis in childhood. It is generally caused by the c.985C > T variant in the BSCL2 gene, leading to the skipping of exon 7 and resulting in an aberrant seipin protein (Celia-seipin).To precisely define the temporal evolution and the mechanisms involved in neurodegeneration, lipodystrophy and fatty liver in Celia's encephalopathy, our group has generated the first global knock-in murine model for the aberrant human transcript of BSCL2 (Bscl2Celia/Celia) using a strategy based on the Cre/loxP recombination system. In order to carry out a characterization at the neurological, adipose tissue and hepatic level, behavioral studies, brain PET, metabolic, histological and molecular studies were performed.Around 12% of homozygous and 5.4% of heterozygous knock-in mice showed severe neurological symptoms early in life, and their life expectancy was dramatically reduced. Severe generalized lipodystrophy and mild hepatic steatosis were present in these affected animals, while serum triglycerides and glucose metabolism were normal, with no insulin resistance. Furthermore, the study revealed a reduction in brain glucose uptake, along with patchy loss of Purkinje cells and the presence of intranuclear inclusions in cerebellar cortex cells. Homozygous, non-severely-affected knock-in mice showed a decrease in locomotor activity and greater anxiety compared with their wild type littermates.Bscl2Celia/Celia is the first murine model of Celia's encephalopathy which partially recapitulates the phenotype and severe neurodegenerative picture suffered by these patients. This model will provide a helpful tool to investigate both the progressive encephalopathy with/without lipodystrophy and congenital generalized lipodystrophy.
PB Elsevier
YR 2023
FD 2023
LK http://hdl.handle.net/10347/32334
UL http://hdl.handle.net/10347/32334
LA eng
NO We are indebted to José Ángel Hernández-Malagón for technical assistance.
DS Minerva
RD 28 abr 2026