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Dental-skeletal-retinal-anomaly (DSRA) is a newly described collagenopathy in Cane Corso dogs. The causative mutation has been linked with splice defects within the melanoma inhibitory activity member 3 (MIA/3) gene that codes for the TANGO1 protein. This case series presents the first dental-related radiographic and histopathological abnormalities in two dogs with genetically confirmed DSRA. The clinical, radiological, and histological features are similar to those reported for MIA3/TANGO1 splice defects previously reported in humans and knockout mice. Common clinical features of these patients include generalized opalescent discoloration of the permanent dentition (intrinsic dyschromia), enamel defects, fractured teeth, vision loss, shortened physical stature, and orthopedic abnormalities that resulted in chronic, early-onset lameness. Intraoral radiography revealed delayed dentin deposition, evidence of endodontic disease, and dental hard tissue loss in both cases. Histopathologic findings for both cases were consistent with dentinogenesis imperfecta (DGI). DSRA exhibits autosomal recessive heritability and commercial diagnostic tests are now available. Clinicians should be aware of the etiopathogenesis, genetic inheritance and associated comorbidities in order to treat and counsel clients on the management of this condition. It is recommended that all breeding individuals be tested, and carriers be sterilized or omitted from the breeding population. This case study describes intraoral diagnoses, treatments, and follow-up of two DSRA-positive dogs. [ABSTRACT FROM AUTHOR]

Dentinogenesis imperfecta is a rare, autosomal dominant, hereditary disorder that occurs in humans and animals. In humans, known causative genetic mutations have been elucidated; however, veterinary literature on the topic is limited. This case report describes a 1-year-old female Labrador Retriever who presented for evaluation of generalized discoloration of the permanent dentition with historical discoloration of the deciduous dentition. Radiographic and histopathological findings will be discussed, as well as an in-depth review of the current human and veterinary literature pertaining to the pathogenesis and treatment options for dentinogenesis imperfecta. [ABSTRACT FROM AUTHOR]

This review describes the clinical, radiographic and histologic characteristics of dentinogenesis imperfecta diagnosed in two unrelated young dogs without evidence of concurrent osteogenesis imperfecta. The dentition was noted to have generalized coronal discoloration ranging from grey-blue to golden brown. Clinical pulp exposure, coronal wear and fractures were observed as was radiographic evidence of endodontic disease, thin dentin walls or dystrophic obliteration of the pulp canal. The enamel was severely affected by attrition and abrasion despite histologically normal areas; loss was most likely due to poor adherence or support by the underlying abnormal dentin. Histologically, permanent and deciduous teeth examined showed thin, amorphous dentin without organized dentin tubules and odontoblasts had dysplastic cell morphology. Primary dentin disorders, including dentinogenesis imperfecta and dentin dysplasia, have been extensively studied and genetically characterized in humans but infrequently reported in dogs. Treatment in human patients is aimed at early recognition and multi-disciplinary intervention to restore and maintain normal occlusion, aesthetics, mastication and speech. Treatment in both humans and canine patients is discussed as is the documented genetic heritability of primary dentin disorders in humans. [ABSTRACT FROM AUTHOR]

Dentin sialophosphoprotein (DSPP) is an extracellular matrix protein highly expressed by odontoblasts in teeth. DSPP mutations in humans may cause dentinogenesis imperfecta (DGI), an autosomal dominant dentin disorder. We recently generated a mouse model (named "DsppP19L/+ mice") that expressed a mutant DSPP in which the proline residue at position 19 was replaced by a leucine residue. We found that the DsppP19L/+ and DsppP19L/P19L mice at a younger age displayed a tooth phenotype resembling human DGI type III characterized by enlarged dental pulp chambers, while the teeth of older DsppP19L/+ and DsppP19L/P19L mice had smaller dental pulp chambers mimicking DGI type II. The teeth of DsppP19L/+ and DsppP19L/P19L mice had a narrower pulp chamber roof predentin layer, thinner pulp chamber roof dentin, and thicker pulp chamber floor dentin. In addition, these mice also had increased enamel attrition, accompanied by excessive deposition of peritubular dentin. Immunohistochemistry, in situ hybridization, and real-time polymerase chain reaction analyses showed that the odontoblasts in both DsppP19L/+ and DsppP19L/P19L mice had reduced DSPP expression, compared to the wild-type mice. We also observed that the levels of DSPP expression were much higher in the roof-forming odontoblasts than in the floor-forming odontoblasts in the wild-type mice and mutant mice. Moreover, immunohistochemistry showed that while the immunostaining signals of dentin sialoprotein (N-terminal fragment of DSPP) were decreased in the dentin matrix, they were remarkably increased in the odontoblasts of the DsppP19L/+ and DsppP19L/P19L mice. Consistently, our in vitro studies showed that the secretion of the mutant DSPP was impaired and accumulated within endoplasmic reticulum. These findings suggest that the dental phenotypes of the mutant mice were associated with the intracellular retention of the mutant DSPP in the odontoblasts of the DSPP-mutant mice. [ABSTRACT FROM AUTHOR]

Secreted WNT proteins control cell differentiation and proliferation in many tissues, and NOTUM is a secreted enzyme that modulates WNT morphogens by removing a palmitoleoylate moiety that is essential for their activity. To better understand the role this enzyme in development, the authors produced NOTUM-deficient mice by targeted insertional disruption of the Notum gene. The authors discovered a critical role for NOTUM in dentin morphogenesis suggesting that increased WNT activity can disrupt odontoblast differentiation and orientation in both incisor and molar teeth. Although molars in Notum-/- mice had normal-shaped crowns and normal mantle dentin, the defective crown dentin resulted in enamel prone to fracture during mastication and made teeth more susceptible to endodontal inflammation and necrosis. The dentin dysplasia and short roots contributed to tooth hypermobility and to the spread of periodontal inflammation, which often progressed to periapical abscess formation. The additional incidental finding of renal agenesis in some Notum -/- mice indicated that NOTUM also has a role in kidney development, with undiagnosed bilateral renal agenesis most likely responsible for the observed decreased perinatal viability of Notum-/- mice. The findings support a significant role for NOTUM in modulating WNT signaling pathways that have pleiotropic effects on tooth and kidney development. [ABSTRACT FROM AUTHOR]

Certain mutations in the COL1A1 and COL1A2 genes produce clinical symptoms of both osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS) that include abnormal craniofacial growth, dental malocclusion, and dentinogenesis imperfecta. A mouse model (Col1a1(Jrt)/+) was recently developed that had a skeletal phenotype and other features consistent with moderate-to-severe OI and also with EDS. The craniofacial phenotype of 4- and 20-wk-old Col1a1(Jrt)/+ mice and wild-type littermates was assessed by micro-computed tomography (µCT) and morphometry. Teeth and the periodontal ligament compartment were analyzed by µCT, light microscopy/histomorphometry, and electron microscopy. Over time, at 20 wk, Col1a1(Jrt)/+ mice developed smaller heads, a shortened anterior cranial base, class III occlusion, and a mandibular side shift with shorter morphology in the masticatory region (maxilla and mandible). Col1a1(Jrt)/+ mice also had changes in the periodontal compartment and abnormalities in the dentin matrix and mineralization. These findings validate Col1a1(Jrt)/+ mice as a model for OI and EDS in humans. [ABSTRACT FROM AUTHOR]

Transforming growth factor β (TGF-β) signaling has been implicated in dentin formation and repair; however, the molecular mechanisms underlying dentin formation remain unclear. To address the role of TGF-β signaling in dentin formation, we analyzed odontoblast-specific Tgfbr2 conditional knockout mice. The mutant mice had aberrant teeth with thin dysplastic dentin and pulpal obliteration, similar to teeth from human patients with dentinogenesis imperfecta type II and dentin dysplasia. In mutant, the odontoblasts lost their cellular polarity, and matrix secretion was disrupted after mantle dentin formation. As a consequence, the amount of predentin decreased significantly, and an ectopic fibrous matrix was formed below the odontoblast layer. This matrix gradually calcified and obliterated the pulp chamber with increasing age. Immunohistochemistry revealed decreased expression of alkaline phosphatase in mutant odontoblasts. In mutant dentin, Dsp expression was reduced, but Dmp1 expression increased significantly. Collagen type I, biglycan, and Dsp were expressed in the ectopic matrix. These results suggest that loss of responsiveness to TGF-β in odontoblasts results in impaired matrix formation and pulpal obliteration. Our study indicates that TGF-β signaling plays an important role in dentin formation and pulp protection. Furthermore, our findings may provide new insight into possible mechanisms underlying human hereditary dentin disorders and reparative dentin formation. [ABSTRACT FROM PUBLISHER]

Objective: To radiographically evaluate the prevalence of tooth abnormalities of number and position in the permanent dentition of individuals with complete bilateral cleft lip and palate. Design: Cross-sectional retrospective. Setting: Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo, Bauru, Brazil. Patients: Two hundred five individuals with complete bilateral cleft lip and palate. Interventions: Analysis of patient records and panoramic radiographs. Main outcome measures: Evaluation of hypodontia and supernumerary teeth and analysis of the position of the permanent maxillary lateral incisor in relation to the alveolar cleft. Results: Hypodontia was observed in 144 patients (70.2%), and the highest prevalence was observed for the maxillary lateral incisor. When both lateral incisors were present (43%), they were primarily located on the distal side of the cleft (25%). Supernumerary teeth were observed in 11.7% of individuals. Conclusion: Patients with cleft lip and palate presented high prevalence of hypodontia and supernumerary teeth. The prevailing characteristics of their location may suggest the presence of a similar genetic component for the occurrence of hypodontia and cleft. [ABSTRACT FROM AUTHOR]

Amelogenesis imperfecta (AI) is a genetically and phenotypically heterogeneous genetic disorder affecting tooth enamel without other non-oral syndromic conditions. Based on a review of the literature, the authors constructed a candidate-gene-based mutational analysis strategy. To test the strategy, they identified two Turkish families with hypoplastic enamel without any other non-oral syndromic phenotype. The authors analyzed all exons and exon/intron boundaries of the enamelin (ENAM) gene for family 1 and the DLX3 and ENAM genes for family 2, to identify the underlying genetic etiology. The analysis revealed 2 ENAM mutations (autosomal-dominant g.14917delT and autosomalrecessive g.13185-13186insAG mutations). A single T deletion in exon 10 is a novel deletional mutation (g.14917delT, c.2991delT), which is predicted to result in a frameshift with a premature termination codon (p.L998fsX1062). This result supports the use of a candidate-gene-based strategy to study the genetic basis for AI. [ABSTRACT FROM AUTHOR]

Hereditary dentin defects are divided into dentinogenesis imperfecta and dentin dysplasia. We identified a family segregating severe dentinogenesis imperfecta. The kindred spanned four generations and showed an autosomal-dominant pattern of inheritance. The proband was a child presenting with a severely affected primary dentition, with wide-open pulp chambers and multiple pulp exposures, resembling a DGI type III (DGI-III) pattern. We hypothesized that a mutation in the DSPP gene is responsible for this severe phenotype. Mutational analyses revealed a novel mutation (c.53T>A, p.V18D) near the intron-exon boundary in the third exon of the DSPP gene. We analyzed the effect of the mutation by means of an in vitro splicing assay, which revealed that the mutation did not affect pre-mRNA splicing. Further studies are needed for a better understanding of the nature of the disease and the development of an appropriate treatment strategy. [ABSTRACT FROM AUTHOR]

Dentinogenesis imperfecta (DGI) and dentin dysplasia (DD) are allelic disorders due to mutations in DSPP. Typically, the phenotype breeds true within a family. Recently, two reports showed that 3 different net -1 bp frameshift mutations early in DSPP's repeat domain caused DD, whereas 6 more 39 frameshift mutations were associated with DGI. Here we identify a DD kindred with a novel -1 bp frameshift (c.3141de1C) that falls within the portion of the DSPP repeat domain previously associated solely with the DGI phenotype. This new frameshift mutation shows that overlapping DSPP mutations can give rise to either DGI or DD phenotypes. Furthermore, the consistent kindred presentation of the DD or DGI phenotype appears to be dependent on an as-yet-undescribed genetic modifier closely linked to DSPP. [ABSTRACT FROM AUTHOR]

Feline inductive odontogenic tumour (FIOT) is a rare and interesting odontogenic neoplasm in which the odontogenic epithelium has inductive potential to form aggregated foci of dental pulp-like mesenchymal cells. Two male cats aged 11 and 10 months presented with nasal swelling and a left maxillary mass. Histopathologically, the masses consisted of non-encapsulated invasive neoplasms exhibiting proliferation of epithelial and mesenchymal components with local infiltration into the maxillary bone in both cases. The epithelial component formed islands, anastomosing strands, and solid sheets of polygonal epithelial cells. Occasionally, these cells formed circular aggregates, resembling the cap stage of odontogenesis. Type IV collagen and laminin were constantly positive around the foci of epithelial cells, and Ki-67 positive indices were extremely low; therefore, these findings consistent with the benign clinical presentation of FIOT. [Copyright &y& Elsevier]

Proteolytic enzymes are necessary for the mineralization of dental enamel during development, and mutations in the kallikrein 4 (KLK4) and enamelysin (MMP20) genes cause autosomal-recessive amelogenesis imperfecta (ARAI). So far, only one KLK4 and two MMP20 mutations have been reported. We have identified an ARAI-causing point mutation (c.102G>A, g.102G>A, and p.W34X) in exon 1 of MMP20 in a proband with autosomal-recessive hypoplastichypomaturation amelogenesis imperfecta. The G to A transition changes the tryptophan (W) codon (TGG) at amino acid position 34 into a translation termination (X) codon (TGA). No disease-causing sequence variations were detected in KLK4. The affected enamel is thin, with mild spacing in the anterior dentition. The enamel layer is hypomineralized, does not contrast with dentin on radiographs, and tends to chip away from the underlying dentin. An intrinsic yellowish pigmentation is evident, even during eruption. The phenotype supports current ideas concerning the function of enamelysin. [ABSTRACT FROM AUTHOR]

By the Shields classification, articulated over 30 years ago, inherited dentin defects are divided into 5 types: 3 types of dentinogenesis imperfecta (DGI), and 2 types of dentin dysplasia (DD). DGI type I is osteogenesis imperfecta (OI) with DGI. OI with DGI is caused, in most cases, by mutations in the 2 genes encoding type I collagen. Many genes are required to generate the enzymes that catalyze collagen's diverse post-translational modifications and its assembly into fibers, fibrils, bundles, and networks. Rare inherited diseases of bone are caused by defects in these genes, and some are occasionally found to include DGI as a feature. Appreciation of the complicated genetic etiology of DGI associated with bony defects splintered the DGI type I description into a multitude of more precisely defined entities, all with their own designations. In contrast, DD-II, DGI-II, and DGI-III, each with its own pattern of inherited defects limited to the dentition, have been found to be caused by various defects in DSPP (dentin sialophospho - protein), a gene encoding the major non-collagenous proteins of dentin. Only DD-I, an exceedingly rare condition featuring short, blunt roots with obliterated pulp chambers, remains untouched by the revolution in genetics, and its etiology is still a mystery. A major surprise in the characterization of genes underlying inherited dentin defects is the apparent lack of roles played by the genes encoding the less-abundant non-collagenous proteins in dentin, such as dentin matrix protein 1 (DMP1), integrin-binding sialoprotein (IBSP), matrix extracellular phosphoglyco - protein (MEPE), and secreted phosphoprotein-1, or osteopontin (SPP1, OPN). This review discusses the development of the dentin extracellular matrix in the context of its evolution, and discusses the phenotypes and clinical classifications of isolated hereditary defects of tooth dentin in the context of recent genetic data respecting their genetic etiologies. [ABSTRACT FROM AUTHOR]

We used the evolutionary analysis of amelogenin (AMEL) in 80 amniotes (52 mammalian and 28 reptilian sequences) to aid in the genetic diagnosis of X-linked amelogenesis imperfecta (AIH1). Out of 191 residues, 77 were found to be unchanged in mammals, and only 34 in amniotes. The latter are considered crucial residues for enamel formation, while the 43 residues conserved only in mammals could indicate that they play new, important roles for enamel formation in this lineage. The 5 substitutions leading to AIH1 were validated when the mammalian dataset was used, and 4 of them with the amniote dataset. These 2 sequence datasets will facilitate the validation of any human AMEL mutation suspected of involvement in AIH1. This evolutionary analysis also revealed numerous residues that appeared to be important for correct AMEL function, but their role remains to be elucidated. [ABSTRACT FROM AUTHOR]

Dentinogenesis imperfecta (DGI) and dentin dysplasia (DD) are allelic disorders that primarily affect the formation of tooth dentin. Both conditions are autosomal-dominant and can be caused by mutations in the dentin sialophospho-protein gene (DSPP, 4q21.3). We recruited 23 members of a four-generation kindred, including ten persons with dentin defects, and tested the hypothesis that these defects are linked to DSPP. The primary dentition showed amber discoloration, pulp obliteration, and severe attrition. The secondary dentition showed either pulp obliteration with bulbous crowns and gray discoloration or thistle-tube pulp configurations, normal crowns, and mild gray discoloration. Haplotype analyses showed no recombination between three 4q21-q24 markers and the disease locus. Mutational analyses identified no coding or intron junction sequence variations associated with affection status in DMP1, MEPE, or the DSP portion of DSPP. The defects in the permanent dentition were typically mild and consistent with a diagnosis of DD-II, but some dental features associated with DGI-II were also present. We conclude that DD-II and DGI-II are milder and more severe forms, respectively, of the same disease. [ABSTRACT FROM AUTHOR]

This case report describes a patient's severe Class III malocclusion, managed with a combination of orthodontic and orthognathic treatment. The medical history was complicated by osteogenesis imperfecta and dentinogenesis imperfecta. In addition the patient was a Jehovah's Witness. Patients with osteogenesis imperfecta carry an increased risk of perioperative haemorrhage, and this led to bimaxillary surgery being carried out as two discrete surgical episodes for the patient described. In addition, the risk of enamel fracture led to orthodontic bands being cemented on all teeth. In spite of the increased risks a successful outcome was achieved. [ABSTRACT FROM AUTHOR]

Amelogenesis imperfecta (AI) is currently classified into 14 distinct subtypes based on various phenotypic criteria; however, the gene responsible for each phenotype has not been defined. We performed molecular genetic studies on a Japanese family with a possible autosomaldominant form of AI. Previous studies have mapped an autosomal-dominant human AI locus to chromosome 4q11-q21, where two candidate genes, ameloblastin and enamelin, are located. We studied AI patients in this family, focusing on these genes, and found a mutation in the enamelin gene. The mutation detected was a heterozygous, single-G deletion within a series of 7 G residues at the exon 9-intron 9 boundary of the enamelin gene. The mutation was detected only in AI patients in the family and was not detected in other unaffected family members or control individuals. The male proband and his brother showed hypoplastic enamel in both their deciduous and permanent teeth, and their father showed local hypoplastic defects in the enamel of his permanent teeth. The clinical phenotype of these patients is similar to that of the first report of AI caused by an enamelin gene mutation. Thus, heterogeneous mutations in the enamelin gene are responsible for an autosomal-dominant hypoplastic form of AI. [ABSTRACT FROM AUTHOR]

Interleukin-1α (IL-1α) is strongly expressed in odontogenic keratocysts. In this study, we investigated the effects of IL-1α on the activation of matrix metalloproteinase-2 (MMP-2) in the fibroblasts isolated from odontogenic keratocysts. Odontogenic keratocyst fibroblasts secreted a latent form of MMP-2 (proMMP-2) spontaneously. Type I collagen induced the activation of the proMMP-2, and recombinant human IL-1α (rhIL-1α) further enhanced the type I collagen-induced activation of proMMP-2 in a dose-dependent manner. The rhIL-1α-induced activation of proMMP-2 was inhibited by antihuman IL-1α antibody. A reverse-transcription/polymerase chain-reaction (RT-PCR) and Western immunoblotting demonstrated that the expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) mRNA and protein was increased in the fibroblasts when the cells were cultured on type I collagen, and the expression was further enhanced by rhIL-1α. Thus, IL-1α may up-regulate proMMP-2 activation by increasing the expression of MT1- MMP in the fibroblasts isolated from odontogenic keratocysts synergistically with type I collagen. [ABSTRACT FROM AUTHOR]

Two case reports illustrate the effective treatment of Class II division 2 malocclusion with modifications to the Twin Block appliance. This approach may reduce the total treatment time and reduce the need for extra-oral anchorage. In each of the cases presented treatment has been carried out on a non-extraction basis with full correction of the malocclusion. [ABSTRACT FROM AUTHOR]

Degenerate oligonucleotides to consensus serine kinase functional domains previously identified a novel, partial rabbit tooth cDNA (Zeichner-David et al., 1992) that was used in this study to identify a full-length mouse clone. A 1390-base-pair cDNA clone was isolated encoding a putative 260-amino-acid open reading frame containing a hydrophobic 25-amino-acid potential transmembrane domain. This clone shares some homology with the TGF-β type I receptor family, but lacks the intracellular kinase domain. DNA database analysis revealed that this clone has 86% identity to a newly isolated human gene termed non-meta-static gene A and 80% identity to a Xenopus cDNA clone termed BMP and activin membrane bound inhibitor. Here we report the mouse Nma/BAMBI cDNA sequence, the tissue expression pattern, and confirmed expression in dental cell lines. This study demonstrates that Nma/BAMBI is a highly conserved protein across species and is expressed at high levels during odontogenesis. [ABSTRACT FROM AUTHOR]

High-resolution synchrotron radiation computed tomography (SRCT) and small-angle x-ray scattering (SAXS) were performed on normal and dentinogenesis imperfecta type II (DI-II) teeth. The SRCT showed that the mineral concentration was 33% lower on average in the DI-II dentin with respect to normal dentin. The SAXS spectra from normal dentin exhibited low-angle diffraction peaks at harmonics of 67.6 nm, consistent with nucleation and growth of the apatite phase within gaps in the collagen fibrils (intrafibrillar mineralization). In contrast, the low-angle peaks were almost non-existent in the DI-II dentin. Crystallite thickness was independent of location in both DI-II and normal dentin, although the crystallites were significantly thicker in DI-II dentin (6.8 nm [SD =0.5] vs. 5.1 nm [SD =0.6]). The shape factor of the crystallites, as determined by SAXS, showed a continuous progression in normal dentin from roughly one-dimensional (needle-like) near the pulp to two-dimensional (plate-like) near the dentin-enamel junction. The crystallites in DI-II dentin, on the other hand, remained needle-like throughout. The above observations are consistent with an absence of intrafibrillar mineral in DI-II dentin. [ABSTRACT FROM AUTHOR]

Dentinogenesis Imperfecta type II (DGI-II) is a localized form of mesodermal dysplasia of the dentin affecting both the primary and permanent dentitions. This is an autosomal-dominant disease in which there is a disorder in dentin mineralization. Several studies have localized DGI-II to human chromosome 4 in the region 4q 12-21. Many ECM genes--such as OPN, DMP1, DMP2, DMP3 (DSPP), and BSP--have been mapped to the same locus. Biochemical studies indicated that dentin phosphophoryn (DMP2) might be a candidate gene in DGI-II. In this study, we have used histological and RFLP analyses of tissues from a DGI-II-affected patient, as compared with two normal controls, to determine if DMP1, 2, or 3 was linked to DGI-II. The histology of the affected tooth was very different in the DGI-II patient as compared with the normals. In particular, the dentinal tubules in the DGI-II patient were very irregular, which could be the result of perturbations in the process of dentin formation. Patient and control DNA samples were digested with EcoRI or PstI and Southern-hybridized with the DMP1, DMP2, and DMP3 cDNAs. Few differences in the restriction pattern were observed between affected and normal samples for DMP1 and DMP3-3 region (phosphophoryn-like sequences) probes. On the other hand, DMP2 showed a dramatic shift in the restriction pattern in DGI-II. This study suggests that the different restriction enzyme digestion profiles of the DNA from the DGI-II patient, as probed by DMP2, might be related to the defective mineralization of dentin in DGI-II. [ABSTRACT FROM AUTHOR]

Dentinogenesis imperfecta type III (DGI-III) is an autosomal-dominant disorder of dentin formation which appears in a tri-racial southern Maryland population known as the "Brandywine isolate". This disease has suggestive evidence of linkage to the long arm of human chromosome 4 (LOD score of 2.0) in a family presenting with both juvenile periodontitis and DGI-III. The purpose of this study was to screen a family presenting with only DGI-III to determine if this locus was indeed on chromosome 4q. Furthermore, we wanted to determine if DGI-III co-localized with dentinogenesis imperfecta type II (DGI-II), which has been localized to 4q21-q23. Therefore, a large kindred from the Brandywine isolate was identified, oral examination performed, and blood samples collected from 21 family members. DNA from this family was genotyped with 6 highly polymorphic markers that span the DGI-II critical region of chromosome 4q. Analysis of the data yielded a maximum two-point LOD score of 4.87 with a marker for the dentin matrix protein 1 (DMP1) locus, a gene contained in the critical region for DGI-II. Our results demonstrated that the DGI-III locus is on human chromosome 4q21 within a 6.6 cM region that overlaps the DGI-II critical region. These results are consistent with the hypothesis that DGI-II is either an allelic variant of DGI-III or the result of mutations in two tightly linked genes. [ABSTRACT FROM AUTHOR]

Dentinogenesis imperfecta type II is an autosomal-dominant disorder of dentin formation which has been mapped to the 6.6 centiMorgan D4S2691-D4S2692 interval at human chromosome 4q21. In the current investigation, the use of four short tandem repeat polymorphisms has allowed the critical region to be refined to an interval of less than 2 centiMorgans defined by recombination events in unrelated, affected individuals from two families both of which show independent evidence for linkage to chromosome 4q21. The creation of a yeast artificial chromosome contig of this newly defined interval has allowed us to demonstrate that the critical region encompasses approximately 2 Mb of DNA and that the dentin-specific gene, dentin sialoprotein, maps to this interval within 300 kb of dentin matrix acidic phosphoprotein 1 and bone sialoprotein. Moreover, dentin sialoprotein shows no recombination with the dentinogenesis imperfecta type II phenotype. Dentin sialoprotein is therefore a candidate for the dentinogenesis imperfecta type II locus. [ABSTRACT FROM AUTHOR]

The epithelial-mesenchymal junctional area in tooth germs of one- and three-year-old Japanese monkeys was studied with electron microscopy. The plasma membranes at the distal ends of inner enamel epithelium cells were relatively even, and were associated with basement membrane. A large number of filaments, which were 15 nm in diameter and up to 2 p~m in length, were present, extending perpendicularly from the basement membrane toward the dental papilla, forming an unique fibrillar layer. The distal cytoplasm of the cell contained rather few vesicles and granules which were positive for the acid phosphatase reaction. The distal ends of differentiating ameloblasts showed irregular undulations and numerous small processes which penetrated through the basement membrane and fibrillar layer. Following an increase of the undulations, the fibrillar layer and the basement membrane were engulfed by the cells and removed from the surface of pre-dentin. Large irregular bodies, which were filled with the filaments of the disintegrating fibrillar layer, were observed frequently. The distal cytoplasm contained a large number of coated pits, coated vesicles, and acid-phosphatase-positive granules. The fibrillar layer then disappeared, being replaced by collagen fibrils in the pre-dentin, which was in the stage of early mineralization. These results indicate that the fibrillar layer is removed by the differentiating ameloblasts and degraded through an engulfing system which is formed by the cell surfaces. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a heterogeneous group of heritable connective tissue disorders, assigned to different mutations in type I collagen genes. A variety of structural abnormalities of dentin have been described in dentinogenesis imperfecta (DI) associated with OI. To clarify further the constitution of the dentin matrix in OI, we immunostained frozen and paraffin sections of deciduous teeth from four patients, each from a different family, with two monoclonal antibodies (MAbs) to the matrix glycoprotein tenascin-C (TN-C). One of the MAbs recognizes an epitope common to all TN-C isoforms (BC-4), and the other is specific for a splicing variant (BC-2). Normal teeth, oral mucosa, and skin were analyzed for comparison. Staining patterns with the two MAbs did not differ markedly. Normal dentin matrix and odontoblasts were lacking reactivity, but the pulp stained clearly. TN-C reactivity was present in the dentin matrix of all teeth obtained from two patients with different OI phenotypes and DI, and in one out of three teeth from one patient who also had DI. The reactivity was distributed in layers, but the staining patterns varied from one patient to another and from tooth to tooth. Intratubular staining seen in a tooth from the patient with clinically and histologically normal teeth was comparable with that present in normal deciduous teeth. The variation in TN-C expression suggests that, besides genetic heterogeneity, epigenetic factors could influence the composition of the dentin matrix in OI. [ABSTRACT FROM AUTHOR]

To elucidate the defective dentin formation in osteogenesis imperfecta (01), we analyzed the expression of selected fibronectin (FN) isoforms in the dentin matrix of a patient with dentinogenesis imperfecta (DI) associated with 01, and in normal teeth. Frozen tooth sections were immunostained with three monoclonal antibodies (MAbs). The MAb recognizing the major cell-binding region (f-33), shared by plasma FN (pFN) and cellular FN (cFN), stained the pulp of normal adult permanent teeth intensely, while no reactivity was present in predentin, (demineralized) dentin, or dental cementum. The periodontal ligament stained unevenly. The dentin matrix of the patient with 01 displayed reactive zones, alternating layerwise or concentrically with non-reactive ones. Staining throughout the connective tissue of adult oral mucosa, analyzed for the form of FN present, was intense, and in dermis, which was also studied, it was moderate. Reactivities in dental tissues with the MAb specific for the ED-A region (IST-9), included in cFN but not pFN, were similar to those with MAb f-33. The mucosal connective tissue stained weakly and dermis was negative, except that nerves and endothelia of some large blood vessels stained clearly. The MAb specific for the ED-B segment (BC-1), also included in cFN only, did not stain any of the tissues analyzed. The results suggest that, unlike mucosal and dermal FNs, FNs in the dental tissues are largely cellular, and also that dentin formation in 01 may be completed by successive generations of pulpal fibroblasts differentiated into hard-tissue-forming cells. [ABSTRACT FROM AUTHOR]

The work described considers the effects on calcified tissues of those concentrations of fluoride which are not overtly cyto-toxic, i.e., in the general region of up to 1-2 μmol/L. Plasma fluoride concentrations or those of the cellular environment are considered rather than dietary levels. The effect of fluoride ion on specific stages of tooth and bone development is discussed. Little effect has been observed on the modulation of gene expression as far as odontogenesis is concerned, although there is evidence that fluoride could be osteogenic in both embryonic and adult tissues. Expression of extracellular matrix protein genes seems not to be impaired, but subtle changes detected in the enamel matrix could be due to selective alterations in amino-acid uptake or interference with subsequent protein processing. This could also be due to an extension of the secretory period without concomitant changes in post-secretory matrix processing. Removal of matrix is apparently impaired, with concomitant incomplete maturation. While existing mineral phases can be affected, it is more likely that matrix and or mineral-matrix interaction is the site of action. Explant studies suggest that the effect may be reversible. Inhibition of proteolysis during enamel maturation may account for the reported inhibition of enamel crystal growth. This is supported by the finding that the normally incomplete maturation of porcine enamel is associated with a somewhat greater residual protein content. The use of animal models in the investigation of enamel dysplasia (fluoride-induced or otherwise) should therefore be viewed with caution. [ABSTRACT FROM PUBLISHER]

High resolution TEM, X-ray diffraction analysis, infrared absorption spectroscopy, thermogravimetry, and chemical and electron microprobe analyses showed that in dentinogenesis imperfecta the mineral phase is a carbonated apatite with crystallites of normal size, but less numerous than in normal dentin. Losses of Ca, P, and Mg, and a higher Ca/P ratio and water content were recorded. [ABSTRACT FROM AUTHOR]

Important progress has been made relative to the growth, structure and function of enamel. Better understanding of the epithelial mesenchymal interactions during odontogenesis has been gained through tissue culture, and the predominant role of the dental papilla has been established. Differences between rodent and human amelogenesis have been demonstrated. With radioautography and cytochemistry, a significant amount of new information has been obtained on the metabolism of the ameloblasts, concerning the synthesis of proteins, glycoproteins and proteoglycans, as well as calcium transport. Numerous biochemical investigations have been devoted to developing and mature enamel matrix. The organic components of human adult enamel are mainly constituted of lipids and proteins, but further investigations are still needed to elucidate their precise nature. The so-called key-hole configuration of adult enamel can be questioned when amelogenesis is considered since the tissue does not develop in a prismatic head-tail fashion. The most important results have probably been obtained in the field of individual enamel apatite crystals shape and ultrastructure as well as in the description of the precise patterns of their carious dissolution which bears great similarities to the dissolution of synthetic apatites in acids. [ABSTRACT FROM PUBLISHER]

The article discusses hereditary opalescent dentin and presents histological, chemical, and physical studies of hereditary opalescent dentin. The destruction and discoloration of teeth caused by hereditary opalescent dentin is described. Details are also provided about the dental enamel and cementum from opalescent teeth.

This article discusses the results of a research study conducted to examine what is stated to be the largest family group to exhibit dentinogenesis imperfecta. Over six generations, 34 of 137 studied subjects were affected by dentinogenesis imperfecta. The researchers note that they were interested in observing variation in gene expression against a uniform genetic background.

Odontogenesis is the earliest expression of ectodermal-ectomesenchymal inductive interaction in the vertebrate fossil record. Other vertebrate integumental skeletal structures are later expressions of homologous interactions, which differ in details but use similar developmental processes. These interactions are specific examples of a more generalized interrelationship between epithelium and mesoderm, which may have phylogenetically preceded the origin of odontogenesis. [ABSTRACT FROM AUTHOR]

This article discusses research that used polarized light and microradiography to investigate the development of dental tissues in dentinogenesis imperfecta. X-ray absorption studies focusing on the development of crown dentin The discoveries that dentinogenesis imperfecta destroys the root pulp chamber and fosters the overdevelopment of lacunar cementum are noted.

That primate studies will lead to a better knowledge of human dental development goes without saying. The 32-toothed Old World monkeys have the closest dental affinities to us. But how close? The answer bears on caries research and orthodontic research. The order of tooth formation is now reasonably known for man, but definitively known for not one other primate species. It is reasonable to assume that some of the sequence polymorphisms known for man will be repeated in other primates, but which and to what extent? Once averages seemed enough. Today we know that the average sequence in man or monkey bears little relationship to the variability known to exist. Very likely the different sequences will vary both between species and within lineages. For experimental purposes it may be necessary to select a primate not just reasonably like us but one with specific sequences like our modal sequences. [ABSTRACT FROM AUTHOR]

The article discusses the pathogenesis of the abnormal odontogenesis observed to result from the inoculation of rabbits using the vaccinia virus. The similarity between the reaction of rabbits to vaccinia inoculation and the incisor defects in rats that result from magnesium deficiency, pituitary insufficiency, and parathyroid insufficiency is also noted.

A response to a reader's letter is presented from the authors of the article "The non-collagenous dentin matrix proteins are involved in dentinogenesis imperfecta type II," which appeared in a previous issue of the publication.

A letter is presented from a reader responding to the article "The non-collagenous dentin matrix proteins are involved in dentinogenesis imperfecta type II," which appeared in a previous issue of the publication.