Modeling the neuropsychiatric manifestations of Lowe syndrome using induced pluripotent stem cells: defective F-actin polymerization and WAVE-1 expression in neuronal cells

Molecular Autism
Jesse BarnesHerbert M Lachman

Abstract

Lowe syndrome (LS) is a rare genetic disorder caused by loss of function mutations in the X-linked gene, OCRL, which codes for inositol polyphosphate 5-phosphatase. LS is characterized by the triad of congenital cataracts, neurodevelopmental impairment (primarily intellectual and developmental disabilities [IDD]), and renal proximal tubular dysfunction. Studies carried out over the years have shown that hypomorphic mutations in OCRL adversely affect endosome recycling and actin polymerization in kidney cells and patient-derived fibroblasts. The renal problem has been traced to an impaired recycling of megalin, a multi-ligand receptor that plays a key role in the reuptake of lipoproteins, amino acids, vitamin-binding proteins, and hormones. However, the neurodevelopmental aspects of the disorder have been difficult to study because the mouse knockout (KO) model does not display LS-related phenotypes. Fortunately, the discovery of induced pluripotent stem (iPS) cells has provided an opportunity to grow patient-specific neurons, which can be used to model neurodevelopmental disorders in vitro, as demonstrated in the many studies that have been published in the past few years in autism spectrum disorders (ASD), schizophrenia (SZ), ...Continue Reading

References

Jan 1, 1987·The Journal of Clinical Investigation·D N SilverR L Nussbaum
May 23, 1995·Proceedings of the National Academy of Sciences of the United States of America·X ZhangP W Majerus
Nov 13, 2002·American Journal of Human Genetics·Sharon F Suchy, Robert L Nussbaum
Jan 1, 2005·American Journal of Human Genetics·Richard R HoopesSteven J Scheinman
Dec 5, 2006·European Journal of Medical Genetics·Maria AddisMilena Cau
Dec 13, 2006·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Boris UtschMichael Ludwig
Mar 1, 2008·Biochemical and Biophysical Research Communications·Heather J McCreaPietro De Camilli
Aug 25, 2009·Nature Reviews. Nephrology·Scott J Schurman, Steven J Scheinman
Jan 21, 2010·Physiological Reviews·Juha SaarikangasPekka Lappalainen
Feb 9, 2010·Nature Neuroscience·Akiko Hayashi-TakagiAkira Sawa
Nov 26, 2010·Nature·Zhucheng ChenMichael K Rosen
Dec 25, 2010·Journal of the American Society of Nephrology : JASN·Susan P BothwellRobert L Nussbaum
Apr 15, 2011·Nature·Kristen J BrennandFred H Gage
Sep 9, 2011·PloS One·Adam G GrieveTimothy P Levine
Oct 6, 2011·The EMBO Journal·Mariella VicinanzaMaria Antonietta De Matteis
Jan 3, 2012·Human Molecular Genetics·Irene Barinaga-Rementeria RamirezMartin Lowe
Jul 24, 2012·International Urology and Nephrology·Ramón PecesJulián Nevado
Jan 10, 2013·Journal of Cardiovascular Translational Research·Masayuki Yazawa, Ricardo E Dolmetsch
Jan 29, 2013·Seminars in Cell & Developmental Biology·Michelle C Mendoza
Jun 7, 2013·Journal of Neuroinflammation·Sandra RedlichRoland Nau
Sep 5, 2014·Nature Protocols·Madeline A Lancaster, Juergen A Knoblich
Oct 15, 2014·Molecular Psychiatry·A Oguro-AndoD H Geschwind
Dec 7, 2014·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Florian ReckerMichael Ludwig
Dec 17, 2014·Biochimica Et Biophysica Acta·Leopoldo StaianoMaria Antonietta De Matteis
Feb 15, 2015·Biochimica Et Biophysica Acta·Mark G Waugh
Mar 31, 2015·Journal of Neurochemistry·Maria V Tejada-Simon
Apr 15, 2015·The Journal of Cell Biology·Fubito NakatsuPietro De Camilli

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Citations

Oct 28, 2019·International Journal of Molecular Sciences·Nashwa El Hadidy, Vladimir N Uversky
Sep 12, 2019·Frontiers in Molecular Neuroscience·Padinjat RaghuSankhanil Saha
Nov 27, 2019·World Journal of Stem Cells·Maria Teresa ValentiDonato Zipeto
Apr 23, 2020·Current Psychiatry Reports·Debamitra DasDimitrios Avramopoulos
Dec 30, 2018·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Shyanne PageAbraham Al-Ahmad

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Methods Mentioned

BETA
genotyping
dissection
PCR
Protein Assay
electrophoresis
FRET
exome sequencing
GTPase

Software Mentioned

GeneDx
ImageJ
Zeiss AxioVision

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