A TERATOGENIC EFFECT OF A SULPHONAMIDE IN EXPERIMENTAL ANIMALS.
(25/272)
Sulphamoprine, when given in the diet at levels from 0.025% upwards to pregnant rats and mice, produced abnormalities of eruption of the incisor teeth and of the skull of the offspring. Rabbits are not susceptible to this teratogenic action. (+info)
Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation.
(26/272)
Nance-Horan syndrome (NHS) is an X-linked disorder characterized by congenital cataracts, dental anomalies, dysmorphic features, and, in some cases, mental retardation. NHS has been mapped to a 1.3-Mb interval on Xp22.13. We have confirmed the same localization in the original, extended Australian family with NHS and have identified protein-truncating mutations in a novel gene, which we have called "NHS," in five families. The NHS gene encompasses approximately 650 kb of genomic DNA, coding for a 1,630-amino acid putative nuclear protein. NHS orthologs were found in other vertebrates, but no sequence similarity to known genes was identified. The murine developmental expression profile of the NHS gene was studied using in situ hybridization and a mouse line containing a lacZ reporter-gene insertion in the Nhs locus. We found a complex pattern of temporally and spatially regulated expression, which, together with the pleiotropic features of NHS, suggests that this gene has key functions in the regulation of eye, tooth, brain, and craniofacial development. (+info)
Sox3 is required for gonadal function, but not sex determination, in males and females.
(27/272)
Sox3 is expressed in developing gonads and in the brain. Evolutionary evidence suggests that the X-chromosomal Sox3 gene may be the ancestral precursor of Sry, a sex-determining gene, and Sox3 has been proposed to play a role in sex determination. However, patients with mutations in SOX3 exhibit normal gonadal determination but are mentally retarded and have short stature secondary to growth hormone (GH) deficiency. We used Cre-LoxP targeted mutagenesis to delete Sox3 from mice. Null mice of both sexes had no overt behavioral deficits and exhibited normal GH gene expression. Low body weight was observed for some mice; overgrowth and misalignment of the front teeth was observed consistently. Female Sox3 null mice (-/-) developed ovaries but had excess follicular atresia, ovulation of defective oocytes, and severely reduced fertility. Pituitary (luteinizing hormone and follicle-stimulating hormone) and uterine functions were normal in females. Hemizygous male null mice (-/Y) developed testes but were hypogonadal. Testis weight was reduced by 42%, and there was extensive Sertoli cell vacuolization, loss of germ cells, reduced sperm counts, and disruption of the seminiferous tubules. We conclude that Sox3 is not required for gonadal determination but is important for normal oocyte development and male testis differentiation and gametogenesis. (+info)
Tooth size in dentitions with buccal canine ectopia.
(28/272)
Much interest has been expressed in recent years regarding various features common to dentitions with palatally displaced canines (PDC), particularly in relation to delayed dental development and reduced tooth size. The aims of the present study were to determine whether dentitions with buccally displaced canines (BDC) have features in common, which may be specific for the condition, when compared with PDC dentitions and those with normally erupting canines. Mesiodistal and buccolingual tooth dimensions were determined for 41 subjects with BDC (21 females and 20 males) aged between 11 and 15 years, who formed the experimental sample. The PDC sample was made up of 58 individuals (37 females and 21 males) and the control group comprised 40 age-matched and consecutively treated subjects (20 males and 20 females), exhibiting normally erupted and undisplaced maxillary canines. The results revealed marked sexual dimorphism. Larger-than-average teeth were present in BDC females, whereas the teeth in BDC males were normally sized. Unilaterally affected females had smaller teeth than bilaterally affected females. Tooth size in BDC was consistently larger than in PDC subjects, although the reason was different between the sexes. In females the PDC teeth were normally sized versus large BDC teeth, whereas in the males, the PDC teeth were small and the BDC teeth normal. It is concluded that combining male and female subjects into an overall BDC group obscures important differences that exist between the two sexes. (+info)
Management of talon cusp affecting the primary central incisor: a case report.
(29/272)
Talon cusps are relatively rare dental anomalies that manifest as accessory cusplike structures and project from the cingulum area of the anterior teeth. The condition can occur in both the primary and permanent dentitions. However, the occurrences of anomalous cusps are rather infrequent in the primary dentition. Little has been written about the treatment of talon cusps in the primary dentition compared with their counterparts in the permanent dentition. The purpose of this article was to document the management of a patient with a maxillary primary incisor affected by a talon cusp and the long-term follow up. (+info)
Teething with IKKalpha to make notches.
(30/272)
Sharpe and colleagues unveil a crucial role for NF-kappaB activity in tooth development, and show that IKKalpha functions both within and independently from the NF-kappaB pathway during molar and incisor morphogenesis, respectively (in the February issue of Developmental Cell). (+info)
Constitutively active PTH/PTHrP receptor in odontoblasts alters odontoblast and ameloblast function and maturation.
(31/272)
Parathyroid hormone (PTH)-related protein (PTH-rP) is an important autocrine/paracrine attenuator of programmed cell differentiation whose expression is restricted to the epithelial layer in tooth development. The PTH/PTHrP receptor (PPR) mRNA in contrast is detected in the dental papilla, suggesting that PTHrP and the PPR may modulate epithelial-mesenchymal interactions. To explore the possible interactions, we studied the previously described transgenic mice in which a constitutively active PPR is targeted to osteoblastic cells. These transgenic mice have a vivid postnatal bone and tooth phenotype, with normal tooth eruption but abnormal, widened crowns. Transgene mRNA expression was first detected at birth in the dental papilla and, at 1 week postnatally, in odontoblasts. There was no transgene expression in ameloblasts or in other epithelial structures. Prenatally, transgenic molars and incisors revealed no remarkable change. By the age of 1 week, the dental papilla was widened, with disorganization of the odontoblastic layer and decreased dentin matrix. In addition, the number of cusps was abnormally increased, the ameloblastic layer disorganized, and enamel matrix decreased. Odontoblastic and, surprisingly, ameloblastic cytodifferentiation was impaired, as shown by in situ hybridization and electron microscopy. Interestingly, ameloblastic expression of Sonic Hedgehog, a major determinant of ameloblastic cytodifferentiation, was dramatically altered in the transgenic molars. These data suggest that odontoblastic activation of the PPR may play an important role in terminal odontoblastic and, indirectly, ameloblastic cytodifferentiation, and describe a useful model to study how this novel action of the PPR may modulate mesenchymal/epithelial interactions at later stages of tooth morphogenesis and development. (+info)
Plasminogen mediates the pathological effects of urokinase-type plasminogen activator overexpression.
(32/272)
Increased expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) is associated with different pathological conditions. Both uPAR-mediated signaling and plasmin-catalyzed extracellular proteolysis may contribute to pathogenesis. To evaluate the involvement of plasminogen in such circumstances, we have taken advantage of transgenic mouse models in which overexpression of uPA and/or uPAR in enamel epithelium, basal epidermis, and hair follicles leads to a pathological phenotype; uPA transgenic mice have chalky-white incisors and, when uPAR is co-expressed, develop extensive alopecia, epidermal thickening, and subepidermal blisters. We report here that when these transgenic mice were backcrossed into a plasminogen-deficient (Plg-/-) background, the dental and skin phenotypes appeared completely normal. Heterozygous Plg+/- transgenic mice exhibited a haplo-insufficiency, with an intermediate or normal phenotype. These results do not argue in favor of a role for uPAR-mediated signaling in our experimental model; rather, they demonstrate an essential, dose-dependent, requirement for plasminogen in uPA-mediated tissue alterations. They also support the hypothesis that plasminogen could play a part in certain skin diseases. (+info)