Osteogenic protein-2, OP-2, a new member of the transforming growth factor-@ (TGF-@) superfamily, closely related to the osteogenic/bone morphogenetic proteins, was discovered in mouse embryo and human hippocampus cDNA libraries.The TGF-@ domain of OP-2 shows 74% identity to OP-1, 75% to Vgr-1, and 76% to BMP-5, hence OP-2 may also have bone inductive activity.The genomic locus of OP-2 has seven exons, like OP-1, and spans more than 27 kilobases (kb).In the C-terminal TGF-@ domain, OP-2 has a unique additional cysteine.Mouse embryos express relatively high levels of OP-2 mRNA at 8 days, two species of 3 and 5 kb.A careful study of mRNA expression of the osteogenic proteins in specific organs revealed discrete mRNA species for BMP-3, BMP-4, BMP-5, and BMP-6/Vgr-1 in lung or liver of young and adult mice.OP-1 is expressed in kidney; however, OP-2 and BMP-2 mRNAs were not detected in any organs studied, suggesting an early developmental role.The extended TGF-@' superfamily is widely represented in vertebrates and invertebrates.Examples among vertebrates are the Vg-1 gene product of Xenopus luevis (l), Mullerian inhibiting substance (MIS) (2), the inhibins and activins (3-5) and bone morphogenetic proteins (BMP-2, -3, -4, and -5) (6,7), Vgr-1 (8), and OP-1 (9).More distantly related to these is GDF-1 (growth and differentiation factor-1) (10).Representing the invertebrates are the decapentaplegic protein (DPP) and 60A gene product of Drosophila melanogaster (11,12).Recently, receptors for activin and TGF-@ were cloned and identified as serine threonine kinases (13-15).TGF-@-related proteins are secreted as a pro form, with the C-terminal domain yielding dimeric mature protein (16,25).The C-terminal TGF-@ domain is characterized by conserved
ABSTRACT We report the isolation of a new homeobox gene from Xenopus laevis genomic DNA. The homeodomain sequence is highly diverged from the prototype Antennapedia sequence, and contains a unique histidine residue in the helix that binds to DNA. The homeo-domain is followed by a 65 amino acid carboxy-terminal domain, the longest found to date in any vertebrate homeobox gene. We have raised specific antibodies against an X1Hbox 8-β-gal fusion protein to determine the spatial and temporal expression of this gene. The nuclear protein first appears in a narrow band of the endoderm at stage 33 and develops into expression within the epithelial cells of the pancreatic anlagen and duodenum. Expression within the pan-creatic epithelium persists into the adult frog. This unprecedented restriction to an anteroposterior band of the endoderm suggests that vertebrate homeobox genes might be involved in specifying positional information not only in the neuroectoderm and mesoderm, but also in the endoderm. Our data suggest that X1Hbox 8 may therefore represent the first member of a new class of position-dependent transcription factors affecting endodermal differentiation.
Type IX collagen is a nonfibrillar collagen composed of three gene products, alpha 1(IX), alpha 2(IX), and alpha 3(IX). Type IX molecules are localized on the surface of type II-containing fibrils and consist of two arms, a long arm that is crosslinked to type II collagen and a short arm that projects into the perifibrillar space. In hyaline cartilage, the alpha 1(IX) collagen transcript encodes a polypeptide with a large N-terminal globular domain (NC4), whereas in many other tissues an alternative transcript encodes an alpha 1(IX) chain with a truncated NC4 domain. It has been proposed that type IX molecules are involved in the interaction of fibrils with each other or with other components of the extracellular matrix. To test this hypothesis, we have generated a mouse strain lacking both isoforms of the alpha 1(IX) chain. Homozygous mutant mice are viable and show no detectable abnormalities at birth but develop a severe degenerative joint disease resembling human osteoarthritis.
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