English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Mitochondrial succinate dehydrogenase (SDH) is a component of both the tricarboxylic acid cycle and the electron transport chain. Mutations of SDHD, the first protein of intermediary metabolism shown to be involved in tumorigenesis, lead to the human tumors paraganglioma (PGL) and pheochromocytoma (PC).  SDHD  is remarkable in showing an ‘imprinted’ tumor suppressor phenotype. Mutations of  SDHD  show a very high penetrance in man and we postulated that knockout of  Sdhd  would lead to the development of PGL/PC, probably in aged mice.    Methodology/Principal Findings  We generated a conventional knockout of  Sdhd  in the mouse, removing the entire third exon. We also crossed this mouse with a knockout of  H19 , a postulated imprinted modifier gene of  Sdhd  tumorigenesis, to evaluate if loss of these genes together would lead to the initiation or enhancement of tumor development. Homozygous knockout of  Sdhd  results in embryonic lethality. No paraganglioma or other tumor development was seen in  Sdhd  KO mice followed for their entire lifespan, in sharp contrast to the highly penetrant phenotype in humans. Heterozygous  Sdhd  KO mice did not show hyperplasia of paraganglioma-related tissues such as the carotid body or of the adrenal medulla, or any genotype-related pathology, with similar body and organ weights to wildtype mice. A cohort of  Sdhd / H19  KO mice developed several cases of profound cardiac hypertrophy, but showed no evidence of PGL/PC.    Conclusions  Knockout of  Sdhd  in the mouse does not result in a disease phenotype.  H19  may not be an initiator of PGL/PC tumorigenesis.

Sdhd and Sdhd/H19 Knockout Mice Do Not Develop Paraganglioma or Pheochromocytoma