RT Journal Article
T1 Unexpected obesity, rather than tumorigenesis, in a conditional mouse model of mitochondrial complex II deficiency.
A1 Al Khazal, Fatimah
A1 Kang, Seungwoo
A1 Nelson Holte, Molly
A1 Choi, Doo-Sup
A1 Singh, Ravinder
A1 Ortega-Sáenz, Patricia
A1 López-Barneo, José
A1 Maher, L James
K1 catecholamines
K1 dopaminergic cells
K1 familial paraganglioma
K1 mitochondrial disease
K1 mouse
K1 obesity
K1 succinate dehydrogenase
K1 tyrosine hydroxylase
AB 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 compartment 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 nondiabetic 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.
YR 2020
FD 2020-11-27
LK http://hdl.handle.net/10668/16683
UL http://hdl.handle.net/10668/16683
LA en
DS RISalud
RD Apr 9, 2025