TY - JOUR
T1 - A natural mouse model reveals genetic determinants of systemic capillary leak syndrome (Clarkson disease)
AU - Raza, Abbas
AU - Xie, Zhihui
AU - Chan, Eunice C.
AU - Chen, Wei Sheng
AU - Scott, Linda M.
AU - Robin Eisch, A.
AU - Krementsov, Dimitry N.
AU - Rosenberg, Helene F.
AU - Parikh, Samir M.
AU - Blankenhorn, Elizabeth P.
AU - Teuscher, Cory
AU - Druey, Kirk M.
N1 - Publisher Copyright:
© 2019, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s42003-019-0647-4
DO - 10.1038/s42003-019-0647-4
M3 - Article
C2 - 31701027
AN - SCOPUS:85074259575
SN - 2399-3642
VL - 2
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 398
ER -