Medullary thick ascending limb impairment in the Gla^tmTg(CAG-A4GALT) Fabry model mice.

ABSTRACT: A main feature of Fabry disease is nephropathy, with polyuria an early manifestation; however, the mechanism that underlies polyuria and affected tubules is unknown. To increase globotriaosylceramide (Gb3) levels, we previously crossbred asymptomatic Gla^tm mice with transgenic mice that expressed human Gb3 synthase (A4GALT) and generated the Gla^tmTg(CAG-A4GALT) symptomatic Fabry model mice. Additional analyses revealed that these mice exhibit polyuria and renal dysfunction without remarkable glomerular damage. In the present study, we investigated the mechanism of polyuria and renal dysfunction in these mice. Gb3 accumulation was mostly detected in the medulla; medullary thick ascending limbs (mTALs) were the most vacuolated tubules. mTAL cells contained lamellar bodi

SUBMITTER: Maruyama H 

PROVIDER: S-EPMC6071062 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature