Murine models of erythroid 5ALA synthesis disorders and their conditional synthetic lethal dependency on pyridoxine.

ABSTRACT:

Abstract

X-linked sideroblastic anemia (XLSA) and X-linked protoporphyria (XLPP) are uncommon diseases caused by loss-of-function and gain-of-function mutations, respectively, in the erythroid form of 5-aminolevulinic acid synthetase (ALAS), ALAS2, which encodes the first enzyme in heme biosynthesis. A related congenital sideroblastic anemia (CSA) is due to mutations in SLC25A38 (solute carrier family 25 member A38), which supplies mitochondrial glycine for ALAS2 (SLC25A38-CSA). The lack of viable animal models has limited the studies on pathophysiology and development of therapies for these conditions. Here, using CRISPR-CAS9 gene editing technology, we have generated knockin mouse models that recapitulate the main features of XLSA and XLPP; and using conventional conditional gene

SUBMITTER: Ducamp S 

PROVIDER: S-EPMC11830978 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature