Artículo
Unexpected obesity, rather than tumorigenesis, in a conditional mouse model of mitochondrial complex II deficiency
Autor/es | Al Khazal, Fatimah
Seungwoo, Kang Holte, Molly Nelson Choi, Doo-Sup Singh, Ravinder Ortega Sáenz, Patricia ![]() ![]() ![]() ![]() ![]() ![]() ![]() López Barneo, José ![]() ![]() ![]() ![]() ![]() ![]() ![]() Maher III, James L. |
Departamento | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Fecha de publicación | 2021 |
Fecha de depósito | 2022-07-18 |
Publicado en |
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Resumen | Mutations in any of the genes encoding the four subunits of succinate dehydrogenase (SDH), a mitochondrial membrane-bound enzyme complex that is involved in both the tricarboxylic acid cycle and the electron transport ... Mutations in any of the genes encoding the four subunits of succinate dehydrogenase (SDH), a mitochondrial membrane-bound enzyme complex that is involved in both the tricarboxylic acid cycle and the electron transport chain, can lead to a variety of disorders. Recognized conditions with such mutations include Leigh syndrome and hereditary tumors such as pheochromocytoma and paraganglioma (PPGL), renal cell carcinoma, and gastrointestinal stromal tumor. Tumors appear in SDH mutation carriers with dominant inheritance due to loss of heterozygosity in susceptible cells. Here, we describe a mouse model intended to reproduce hereditary PPGL through Cre-mediated loss of SDHC in cells that express tyrosine hydroxylase (TH), a com-partment where PPGL is known to originate. We report that while there is modest expansion of TH+ glomus cells in the carotid body upon SDHC loss, PPGL is not observed in such mice, even in the presence of a conditional dominant negative p53 protein and chronic hypoxia. Instead, we report an unexpected phenotype of nondia-betic obesity beginning at about 20 weeks of age. We hypothesize that this obesity is caused by TH+ cell loss or altered phenotype in key compartments of the central nervous system responsible for regulating feeding behavior, coupled with metabolic changes due to loss of peripheral catecholamine production. |
Identificador del proyecto | SAF2016-74990-R
![]() ERC-ADGPRJ201502629 ![]() |
Cita | Al Khazal, F., Seungwoo, K., Holte, M.N., Choi, D., Singh, R., Ortega Sáenz, P.,...,Maher III, J.L. (2021). Unexpected obesity, rather than tumorigenesis, in a conditional mouse model of mitochondrial complex II deficiency. Fased Journal, 35 (2), e21227-. |
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