Distinct Functional Requirements for Podocalyxin in Immature and Mature Podocytes Reveal Mechanisms of Human Kidney Disease.

Scientific Reports
Ido RefaeliK M McNagny

Abstract

Dominant and recessive mutations in podocalyxin (PODXL) are associated with human kidney disease. Interestingly, some PODXL mutations manifest as anuria while others are associated with proteinuric kidney disease. PODXL heterozygosity is associated with adult-onset kidney disease and podocalyxin shedding into the urine is a common biomarker of a variety nephrotic syndromes. It is unknown, however, how various lesions in PODXL contribute to these disparate disease pathologies. Here we generated two mouse stains: one that deletes Podxl in developmentally mature podocytes (Podxl∆Pod) and a second that is heterozygous for podocalyxin in all tissues (Podxl+/-). We used histologic and ultrastructural analyses, as well as clinical chemistry assays to evaluate kidney development and function in these strains. In contrast to null knockout mice (Podxl-/-), which die shortly after birth from anuria and hypertension, Podxl∆Pod mice develop an acute congenital nephrotic syndrome characterized by focal segmental glomerulosclerosis (FSGS) and proteinuria. Podxl+/- mice, in contrast, have a normal lifespan, and fail to develop kidney disease under normal conditions. Intriguingly, although wild-type C57Bl/6 mice are resistant to puromycin amino...Continue Reading

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Citations

May 1, 2021·International Journal of Molecular Sciences·Kana Asano-MatsudaJun Matsuda
Oct 7, 2021·Annual Review of Cell and Developmental Biology·Joe Chin-Hun Kuo, Matthew J Paszek
Oct 12, 2021·American Journal of Physiology. Renal Physiology·Shivangi AgarwalMehmet M Altintas

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Methods Mentioned

BETA
glycosylation
transmission electron microscopy
urine collection
exome sequencing
electron microscopy
ELISA
electrophoresis

Software Mentioned

ImageJ

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