Medullary thick ascending limb impairment in the Gla tm Tg(CAG‐A4GALT ) Fabry model mice

What is it about?

Fabry disease is a rare genetic disorder that is caused by mutations in the alpha galactosidase A gene. This mutation results in decreased production of the alpha galactosidase enzyme; consequently, glycosphingolipids, especially globotriaosylceramide (Gb3), accumulate in the body, affecting tissue and organ function, particularly the kidneys. This causes excessive urine excretion (polyuria) in the early stages of Fabry disease. To better understand how this happens, we used a mouse model of this disease and found that Gb3 accumulated mostly tubules in the inner regions (or medulla) of the kidney. Moreover, the structures of tubules in the medulla lost their characteristic shape. This led to fibrosis (scarring and thickening of connective tissue) around the affected tubules. We also found that the kidneys lost their ability to reabsorb water and salt from urine, resulting in the loss of water and salt from the body. These findings mirrored observations in human patients and shed new light on the cause of polyuria in Fabry disease.

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