Functional analysis of Gscl in the pathogenesis of the DiGeorge and velocardiofacial syndromes

UMMS Affiliation

Department of Cell Biology

Publication Date


Document Type



Abnormalities, Multiple; Animals; Brain; DiGeorge Syndrome; Female; Fertility; Gene Deletion; Gene Expression Regulation, Developmental; Goosecoid Protein; Homeodomain Proteins; In Situ Hybridization; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Mutagenesis, Site-Directed; Nuclear Proteins; Pregnancy; Proteins; RNA Probes; *Repressor Proteins; Survival; Syndrome; *Transcription Factors


Cell Biology


Gscl encodes a Goosecoid-related homeodomain protein that is expressed during mouse embryogenesis. In situ hybridization and immunohistochemistry studies show that Gscl is expressed in the pons region of the developing central nervous system and primordial germ cells. Gscl expression is also detected in a subset of adult tissues, including brain, eye, thymus, thyroid region, stomach, bladder and testis. Gscl is located within a region of the mouse genome that is syntenic with the region commonly deleted in DiGeorge and velocardiofacial syndrome (DGS/VCFS) patients. DGS/VCFS patients have craniofacial abnormalities, cardiac outflow defects and hypoplasia of the parathyroid gland and thymus due to haploinsufficiency of a gene or genes located within the deleted region. Thus, the genomic location of Gscl and its expression in a subset of the tissues affected in DGS/VCFS patients suggest that Gscl may contribute to the pathogenesis of DGS/VCFS. To determine the role of Gscl during mouse embryogenesis and in DGS/VCFS, we have deleted Gscl by gene targeting in mouse embryonic stem cells. Both Gscl heterozygous and Gscl null mice were normal and fertile, suggesting that Gscl is not a major factor in DGS/VCFS. Interestingly, expression of the adjacent Es2 gene in the pons region of Gscl null fetuses was absent, suggesting that mutations within the DGS/VCFS region can influence expression of adjacent genes. In addition, embryos that lacked both Gscl and the related Gsc gene appeared normal. These studies represent the first functional analysis of a DGS/VCFS candidate gene in vivo. These Gscl null mice will be an important genetic resource for crosses with other mouse models of the DGS/VCFS.

DOI of Published Version



Hum Mol Genet. 1998 Nov;7(12):1835-40. doi: 10.1093/hmg/7.12.1835

Journal/Book/Conference Title

Human molecular genetics

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PubMed ID