Biomedical subjects

J Terrig Thomas

Publications and source records attributed to J Terrig Thomas.

4 recordsLinked to original sources

PubMed2006

CDMP1/GDF5 has specific processing requirements that restrict its action to joint surfaces.

CDMP1/GDF5 has not demonstrated biological activity in Xenopus embryos when overexpressed by mRNA injection. We provide biological and biochemical evidence that to become active, the protein requires cleavage by two distinct proteolytic enzymes. We demonstrate a specific overlap in the expression patterns of CDMP1/GDF5 with the proteases required to release the mature peptide at the location of the future articular surface but not in the future joint space. Taken together, these observations provide a plausible mechanism for local action of CDMP1/GDF5 consistent with requirements imposed by current models of pattern formation in the developing limb.

Amino Acid Sequence↗

PubMed2004

Characterization of Frzb-Cre transgenic mouse.

The Wnt family of glycoproteins is involved in numerous developmental and disease processes in higher eukaryotes, exerting their action by binding to cell-surface receptors. In the extracellular space, Wnts are negatively regulated by secreted antagonists that either bind to the receptors directly (Dkk1) or to Wnt molecules themselves (Sfrp-FRZB family), preventing its subsequent binding to the receptor. Here we report on a transgenic mouse expressing Cre under the control of the mouse Frzb promoter element. Analysis of the Cre expression was carried out at 10.5 and 14.5 dpc using the ROSA26R mouse line. Expression of the transgenic construct was detected in the limbs, the heart, the nasal epithelium, bone, whiskers, and around the orbita of the eye. The mouse could be used for conditional gene modification in those tissues.

Animals↗

PubMed2002

An enhancer complex confers both high-level and cell-specific expression of the human type X collagen gene.

Type X collagen expression is restricted to hypertrophic chondrocytes in the endochondral growth plate. Transient transfection of reporter constructs containing the human collagen X promoter into primary growth plate chondrocytes identified a cis-acting positive regulatory DNA element(s) that has cell-specific enhancer properties and binds a nuclear protein expressed specifically in growth plate chondrocytes. Functional disruption of this region results in a significant reduction in the activation of reporter gene transcription. The identified enhancer is a major element controlling both high-level and cell-specific expression of type X collagen gene.

Base Sequence↗

PubMed2002

The mutational spectrum of brachydactyly type C.

Growth/differentiation factor-5 (GDF5), also known as cartilage-derived morphogenetic protein-1 (CDMP-1), is a secreted signaling molecule that participates in skeletal morphogenesis. Heterozygous mutations in GDF5, which maps to human chromosome 20, occur in individuals with autosomal dominant brachydactyly type C (BDC). Here we show that BDC is locus homogeneous by reporting a GDF5 frameshift mutation segregating with the phenotype in a family whose trait was initially thought to map to human chromosome 12. We also describe heterozygous mutations in nine additional probands/families with BDC and show nonpenetrance in a mutation carrier. Finally, we show that mutant GDF5 polypeptides containing missense mutations in their active domains do not efficiently form disulfide-linked dimers when expressed in vitro. These data support the hypothesis that BDC results from functional haploinsufficiency for GDF5.

Animals↗