Brain and Eye Malformations Resembling Walker–Warburg Syndrome Are Recapitulated in Mice by Dystroglycan Deletion in the Epiblast

Jakob S Satz; Rita Barresi; Madeleine Durbeej; Tobias Willer; Amy Turner; Steven A Moore; Kevin P Campbell

doi:10.1523/JNEUROSCI.2457-08.2008

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Brain and Eye Malformations Resembling Walker–Warburg Syndrome Are Recapitulated in Mice by Dystroglycan Deletion in the Epiblast

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Brain and Eye Malformations Resembling Walker–Warburg Syndrome Are Recapitulated in Mice by Dystroglycan Deletion in the Epiblast

Jakob S Satz, Rita Barresi, Madeleine Durbeej, Tobias Willer, Amy Turner, Steven A Moore and Kevin P Campbell

The Journal of neuroscience, Vol.28(42), pp.10567-10575

10/15/2008

DOI: 10.1523/JNEUROSCI.2457-08.2008

PMCID: PMC2714190

PMID: 18923033

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Abstract

Walker–Warburg syndrome (WWS) is a severe congenital disease that is characterized by brain and eye malformations and lethality during the first year of life. Genetic mutations have been identified in a subset of WWS patients, but a majority of clinical cases have unknown etiologies. POMT1 and POMT2 , two of the causative genes, form an active enzyme complex in the posttranslational biosynthetic pathway of dystroglycan. Deletion of either Pomt1 or the dystroglycan gene causes early embryonic lethality in mice. Here we report that mice with epiblast-specific loss of dystroglycan develop brain and eye defects that broadly resemble the clinical spectrum of the human disease, including aberrant neuron migration, hydrocephalus, and malformations of the anterior and posterior chambers of the eye. Breaches of basement membranes coincide with the pathology, revealing an important function for dystroglycan in the morphogenesis of the brain and eye. These findings demonstrate the central role of dystroglycan in WWS and suggest that novel defects in posttranslational processing or mutations of the dystroglycan gene itself may underlie cases in which no causative mutation has been found.

congenital muscular dystrophy

Walker–Warburg syndrome

lissencephaly

dystroglycan

hydrocephalus

microphthalmia

Details

Title: Subtitle: Brain and Eye Malformations Resembling Walker–Warburg Syndrome Are Recapitulated in Mice by Dystroglycan Deletion in the Epiblast
Creators: Jakob S Satz - Howard Hughes Medical Institute and
Rita Barresi - Howard Hughes Medical Institute and
Madeleine Durbeej - Howard Hughes Medical Institute and
Tobias Willer - Howard Hughes Medical Institute and
Amy Turner - Howard Hughes Medical Institute and
Steven A Moore - Pathology
Kevin P Campbell - Howard Hughes Medical Institute and
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.28(42), pp.10567-10575
Publisher: Society for Neuroscience
DOI: 10.1523/JNEUROSCI.2457-08.2008
PMID: 18923033
PMCID: PMC2714190
ISSN: 0270-6474
eISSN: 1529-2401
Language: English
Date published: 10/15/2008
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute
Record Identifier: 9984020735302771

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