Genomic characterization and embryonic expression of the mouse Bigh3 (Tgfbi) gene

Mutations in human BIGH3 (TGFB1), a gene identified after treatment of an a denocarcinoma cell line with TGF-P, have been observed in patients with gra nular Groenouw type I, Reis-Bucklers, Thiel-Behnke, Avellino, and Lattice t ype I and IIIa, six autosomal dominant corneal dystrophies linked to chromo some 5q. In order to gain insight into the physiological role of this gene, we characterized the genomic structure of the mouse Bigh3 and its expressi on in murine embryos. The gene spans 30 kb on mouse chromosome 13 and has 1 7 exons. Embryonic expression of Bigh3 is observed in the mesenchyme of the first and second branchial archs as early as dpc 11.5 and is particularly strong in the mesenchyme of numerous tissues throughout all the development stages. In fetal eye, the expression is first seen at 11.5 dpc in the mese nchyme surrounding the optic stalk, extends toward the sclera and choroid b y 14.3 dpc and reaches the cornea by 17.5 dpc. Because the physiological ro le of BIGH3/Bigh3 is still largely unknown, embryonic expression in organs like heart, vessels, and intestine may help to identify new functions which could be searched for in patients and in knock-out animal models. The char acterization of the murine structure is a prerequisite for the making of su ch models. (C) 2000 Academic Press.