Deletion of the GATA Domain of TRPS1 Causes an Absence of Facial Hair and Provides New Insights into the Bone Disorder in Inherited Tricho-Rhino-Phalangeal Syndromes
- 1 December 2002
- journal article
- Published by Informa UK Limited in Molecular and Cellular Biology
- Vol. 22 (24), 8592-600
- https://doi.org/10.1128/mcb.22.24.8592-8600.2002
Abstract
GATA transcription factors mediate cell differentiation in diverse tissues, and their dysfunction is associated with certain congenital human disorders. The six classical vertebrate GATA proteins, GATA-1 to GATA-6, are highly homologous, bear two tandem zinc fingers of the C(4) (GATA) type, and activate transcription. TRPS1, the only other vertebrate protein with the GATA motif, is a large, multitype zinc finger protein that harbors a single DNA-binding GATA domain and represses transcription. Monoallelic TRPS1 mutations cause two dominantly inherited human developmental disorders of the hair, face, and digits, tricho-rhino-phalangeal syndrome (TRPS) types I (MIM 190350) and III (MIM 190351); missense GATA domain mutations account for the more severe type III form. Here we report that heterozygous mice with deletions of the TRPS1 GATA domain (TRPS1(+/Deltagt)) display facial anomalies that overlap with findings for TRPS, whereas TRPS1(Deltagt/Deltagt) mice additionally reveal a complete absence of vibrissae. Unexpectedly, TRPS1(Deltagt/Deltagt) mice die of neonatal respiratory failure resulting from abnormalities of the thoracic spine and ribs. Heterozygotes also develop thoracic kyphoscoliosis with age and reveal structural deficits in cortical and trabecular bones. These findings directly implicate the GATA type zinc finger of TRPS1 in regulation of bone and hair development and suggest that skeletal abnormalities emphasized in descriptions of TRPS are only the extreme manifestations of a generalized bone dysplasia.Keywords
This publication has 66 references indexed in Scilit:
- GATA3 haplo-insufficiency causes human HDR syndromeNature, 2000
- Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1Nature Genetics, 2000
- Direct Three-Dimensional Morphometric Analysis of Human Cancellous Bone: Microstructural Data from Spine, Femur, Iliac Crest, and CalcaneusJournal of Bone and Mineral Research, 1999
- GATA4 haploinsufficiency in patients with interstitial deletion of chromosome region 8p23.1 and congenital heart diseaseAmerican Journal of Medical Genetics, 1999
- Transcription factor GATA-3 is required for development of the T-cell lineageNature, 1996
- In vivo reproducibility of three-dimensional structural properties of noninvasive bone biopsies using 3D-pQCTJournal of Bone and Mineral Research, 1996
- Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesisNature Genetics, 1995
- Tricho‐rhino‐phalangeal syndrome type IIIAmerican Journal of Medical Genetics, 1994
- Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogeneCell, 1991
- Differential staining of cartilage and bone in whole mouse fetuses by alcian blue and alizarin red STeratology, 1980