A mouse model of Townes-Brocks syndrome expressing a truncated mutant sall1 protein is protected from acute kidney injury

Sara Hirsch, Tarek El-Achkar, Lynn Robbins, Jeannine Basta, Monique Heitmeier, Ryuichi Nishinakamura, Michael Rauchman

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5 Scopus citations


It has been postulated that developmental pathways are reutilized during repair and regeneration after injury, but functional analysis of many genes required for kidney formation has not been performed in the adult organ. Mutations in SALL1 cause Townes-Brocks syndrome (TBS) and nonsyndromic congenital anomalies of the kidney and urinary tract, both of which lead to childhood kidney failure. Sall1 is a transcriptional regulator that is expressed in renal progenitor cells and developing nephrons in the embryo. However, its role in the adult kidney has not been investigated. Using a mouse model of TBS (Sall1TBS), we investigated the role of Sall1 in response to acute kidney injury. Our studies revealed that Sall1 is expressed in terminally differentiated renal epithelia, including the S3 segment of the proximal tubule, in the mature kidney. Sall1TBS mice exhibited significant protection from ischemia-reperfusion injury and aristolochic acid-induced nephrotoxicity. This protection from acute injury is seen despite the presence of slowly progressive chronic kidney disease in Sall1TBS mice. Mice containing null alleles of Sall1 are not protected from acute kidney injury, indicating that expression of a truncated mutant protein from the Sall1TBS allele, while causative of congenital anomalies, protects the adult kidney from injury. Our studies further revealed that basal levels of the preconditioning factor heme oxygenase- 1 are elevated in Sall1TBS kidneys, suggesting a mechanism for the relative resistance to injury in this model. Together, these studies establish a functional role for Sall1 in the response of the adult kidney to acute injury.

Original languageEnglish
Pages (from-to)F852-F863
JournalAmerican Journal of Physiology - Renal Physiology
Issue number10
StatePublished - 2015


  • Acute kidney injury
  • Nephrotoxicity
  • Renal hypoplasia
  • Sall1
  • Townes-Brocks syndrome


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