Human Molecular Genetics, Vol 7, 1841-1849, Copyright © 1998 by Oxford University Press
B Saint-Jore, A Puech, J Heyer, Q Lin, C Raine, R Kucherlapati and AI Skoultchi
Velocardiofacial syndrome (VCFS) and DiGeorge syndrome (DGS) are
characterized by a wide spectrum of abnormalities, including conotruncal
heart defects, velopharyngeal insufficiency, craniofacial anomalies and
learning disabilities. In addition, numerous other clinical features have
been described, including frequent psychiatric illness. Hemizygosity for a
1.5-3 Mb region of chromosome 22q11 has been detected in >80% of
VCFS/DGS patients. It is thought that a developmental field defect is
responsible for many of the abnormalities seen in these patients and that
the defect occurs due to reduced levels of a gene product active in early
embryonic development. Goosecoid-like ( GSCL ) is a homeobox gene which is
present in the VCFS/DGS commonly deleted region. The mouse homolog, Gscl,
is expressed in mouse embryos as early as E8.5. Gscl is related to
Goosecoid ( Gsc ), a gene required for proper craniofacial development in
mice. GSCL has been considered an excellent candidate for contributing to
the developmental defects in VCFS/DGS patients. To investigate the role of
Goosecoid-like in VCFS/DGS etiology, we disrupted the Gscl gene in mouse
embryonic stem cells and produced mice that transmit the disrupted allele.
Mice that are homozygous for the disrupted allele appear to be normal and
they do not exhibit any of the anatomical abnormalities seen in VCFS/DGS
patients. RNA in situ hybridization to mouse embryo sections revealed that
Gscl is expressed at E8.5 in the rostral region of the foregut and at E11.5
and E12.5 in the developing brain, in the pons region and in the choroid
plexus of the fourth ventricle. Although the gene inactivation experiments
indicate that haploinsufficiency for GSCL is unlikely to be the sole cause
of the developmental field defect thought to be responsible for many of the
abnormalities in VCFS/DGS patients, its localized expression during
development could suggest that hemizygosity for GSCL, in combination with
hemizygosity for other genes in 22q11, contributes to some of the
developmental defects as well as the behavioral anomalies seen in these
patients. The mice generated in this study should help in evaluating these
possibilities.
ARTICLES
Goosecoid-like (Gscl), a candidate gene for velocardiofacial syndrome, is not essential for normal mouse development
Department of Cell Biology, Department of Molecular Genetics and Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
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