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A natural mouse model reveals genetic determinants of systemic capillary leak syndrome (Clarkson disease).


ABSTRACT: The systemic capillary leak syndrome (SCLS, Clarkson disease) is a disorder of unknown etiology characterized by recurrent episodes of vascular leakage of proteins and fluids into peripheral tissues, resulting in whole-body edema and hypotensive shock. The pathologic mechanisms and genetic basis for SCLS remain elusive. Here we identify an inbred mouse strain, SJL, which recapitulates cardinal features of SCLS, including susceptibility to histamine- and infection-triggered vascular leak. We named this trait "Histamine hypersensitivity" (Hhs/Hhs) and mapped it to Chromosome 6. Hhs is syntenic to the genomic locus most strongly associated with SCLS in humans (3p25.3), revealing that the predisposition to develop vascular hyperpermeability has a strong genetic component conserved between humans and mice and providing a naturally occurring animal model for SCLS. Genetic analysis of Hhs may reveal orthologous candidate genes that contribute not only to SCLS, but also to normal and dysregulated mechanisms underlying vascular barrier function more generally.

SUBMITTER: Raza A 

PROVIDER: S-EPMC6823437 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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A natural mouse model reveals genetic determinants of systemic capillary leak syndrome (Clarkson disease).

Raza Abbas A   Xie Zhihui Z   Chan Eunice C EC   Chen Wei-Sheng WS   Scott Linda M LM   Robin Eisch A A   Krementsov Dimitry N DN   Rosenberg Helene F HF   Parikh Samir M SM   Blankenhorn Elizabeth P EP   Teuscher Cory C   Druey Kirk M KM  

Communications biology 20191031


The systemic capillary leak syndrome (SCLS, Clarkson disease) is a disorder of unknown etiology characterized by recurrent episodes of vascular leakage of proteins and fluids into peripheral tissues, resulting in whole-body edema and hypotensive shock. The pathologic mechanisms and genetic basis for SCLS remain elusive. Here we identify an inbred mouse strain, SJL, which recapitulates cardinal features of SCLS, including susceptibility to histamine- and infection-triggered vascular leak. We name  ...[more]

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