Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on a severe developmental dental defect that results in a dentin dysplasia phenotype with major microdontia, oligodontia, and shape abnormalities in a highly consanguineous family. Homozygosity mapping revealed a unique zone on 6q27-ter. The two affected children were found to carry a homozygous mutation in SMOC2. Knockdown of smoc2 in zebrafish showed pharyngeal teeth that had abnormalities reminiscent of the human phenotype. Moreover, smoc2 depletion in zebrafish affected the expression of three major odontogenesis genes: dlx2, bmp2, and pitx2.
New analogues of JV-acetylmuramyl-L-alanyl-n-isoglutamine (MDP) have been synthesized in which the D-isoglutaminyl residue has been replaced by D-glutamine alkyl esters. They are all adjuvant active; however, their intravenous injection does not induce a febrile response in rabbits at a dose of 10 mg/kg, in contrast to MDP in which the minimal pyrogenic dose is 25 Mg/kg.A chemically well-defined, synthetic, nontoxic compound able to amplify specific and/or nonspecific immune responses would be of paramount therapeutic value. Such an agent might be, among other candidates, AT-acetylmuramyl-L-alanyl-D-isoglutamine (MDP, 1), which has been identified as the minimal structure capable of replacing whole myobacterial cells in complete Freund's adjuvant for enhancing the level of circulating antibodies and producing delayed hypersensitivity against a given antigen.2,3 MDP was found to be adjuvant active in saline4 even when administered by the oral route.5 Moreover, it was shown to increase nonspecific resistance to bacterial infections.6 Since its first synthesis,7 more than 200 papers on the chemistry and biological properties of MDP and its derivatives have been published; for reviews see, ref 8-11. Nevertheless, its potential clinical applications have become somewhat questionable, since it was reported that MDP elicits a febrile response in rabbits12"14 and the release of endogenous pyrogen.15(1) This paper is dedicated to the memory of Professor Frantisek §orm.(2) F.
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