TitleA human stem cell resource to decipher the biochemical and cellular basis of neurodevelopmental defects in Lowe Syndrome.
Publication TypeJournal Article
Year of Publication2022
AuthorsAkhtar BM, Bhatia P, Acharya S, Sharma S, Sharma Y, Aswathy BS, Ganapathy K, Vasudevan A, Raghu P
JournalBiol Open
Date Published2022 Jan 13

Human brain development is a complex process where multiple cellular and developmental events are co-ordinated to generate normal structure and function. Alteration in any of these events can impact brain development, manifesting clinically as neurodevelopmental disorders. Human genetic disorders of lipid metabolism often present with features of altered brain function. Lowe syndrome (LS), is a X-linked recessive disease with features of altered brain function. LS results from mutations in OCRL1 that encodes a phosphoinositide 5-phosphatase enzyme. However, the cellular mechanisms by which loss of OCRL1 leads to brain defects remain unknown. Human brain development involves several cellular and developmental features not conserved in other species and understanding such mechanisms remains a challenge. Rodent models of LS have been generated, but failed to recapitulate features of the human disease. Here we describe the generation of human stem cell lines from LS patients. Further, we present biochemical characterization of lipid metabolism in patient cell lines and demonstrate their use as a "disease-in-a-dish" model for understanding the mechanism by which loss of OCRL1 leads to altered cellular and physiological brain development.

Alternate JournalBiol Open
PubMed ID35023542
Grant ListBT/PR17316/MED/31/326/2015 / / Department of Biotechnology /
Project Identification No. RTI 4006 / / Department of Atomic Energy /
/ / Pratiksha Trust /
IA/S/14/2/501540 / / India Alliance /