Anti-FGF12 monoclonal antibody, clone 2E0

Objective. To investigate and compare the cellular expression of non-secreted Fgf11-14 and secreted Fgf15-18 and -20 mRNAs during tooth formation. Materials and methods. mRNA expression was analyzed from the morphological initiation of the mouse mandibular first molar development to the onset of crown calcification using sectional in situ hybridization. Results. This study found distinct, differentially regulated expression patterns for the Fgf11-13, -15-17 and -20, in particular in the epithelial-mesenchymal interface, whereas Fgf14 and 18 mRNAs were not detected. Fgf11, -15, -16, -17 and -20 were seen in the epithelium, whereas Fgf12 and -13 signals were restricted to the mesenchymal tissue component of the tooth. Fgf11 was observed in the putative epithelial signaling areas, the tertiary enamel knots and enamel free areas of the calcifying crown. Fgf15, Fgf17 and -20 were transiently colocalized in the thickened dental epithelium at E11.5. Later Fgf15 and -20 were exclusively expressed in the epithelial enamel knot signaling centers. In contrast, Fgf13 was present in the dental mesenchyme including odontoblasts cell lineage, whereas Fgf12 appeared transiently in the preodontoblasts. Conclusions. The expression of the Fgf11-13, -15, -17 and -20 in the epithelial signaling centers and/or epithelial-mesenchymal interfaces at key stages of the tooth formation suggest important functions in odontogenesis. Future analyses of the transgenic mice will help elucidate in vivo functions of the studied Fgfs during odontogenesis and whether any of the functions of the tooth expressed epithelial and mesenchymal Fgfs of different sub-families are redundant.

Hereditary non-syndromic sensorineural hearing loss (NSSHL) is a genetically highly heterogeneous group of disorders. Autosomal dominant forms account for up to 20% of cases. To date, 39 loci have been identified by linkage analysis of affected families that segregate NSSHL forms in the autosomal dominant mode (DFNA). Investigation of a large Spanish pedigree with autosomal dominant inheritance of bilateral and progressive NSSHL of postlingual onset excluded linkage to known DFNA loci and, in a subsequent genome-wide scan, the disorder locus was mapped to 3q28-29. A maximum two-point LOD score of 4.36 at theta = 0 was obtained for marker D3S1601. Haplotype analysis placed the novel locus, DFNA44, within a 3-cM genetic interval defined by markers D3S1314 and D3S2418. Heteroduplex analysis and DNA sequencing of coding regions and exon/intron boundaries of two genes (CLDN16 and FGF12) in this interval did not reveal disease-causing mutations.