mortality/aging
• mice show an increased death rate and stress intolerance
|
growth/size/body
• lower incisor pulp is completely obliterated at 6 and 12 months of age; blood vessels and nerve fibers disappear in the distal pulp and there is major loss in cellularity
|
• mice show flattening of the lower incisor tips at 6 and 12 months, but not at 1 month of age, suggesting a defect in abrasion and self-sharpening and/or altered occlusion
• micro-computed tomography of the lower incisors at the height of the first molar showed that the width of the dentin layer is increased at 1 month while incisor pulp is completely obliterated and periodontal space is wider at 6 and 12 months
• severe epithelial and mesenchymal differentiation defects are seen in the apical region of the lower incisors at 3 months
• a soft food diet ameliorates both epithelial and mesenchymal differentiation in the incisor apical region
|
• visible enamel defects in the upper incisors at 12 months of age, with only few enamel spots remaining
|
• in situ hybridization analysis revealed reduced expression of Axin2, Fgf10, and Gli1 in the region of the mesenchymal stem cell niche of the incisors at 1 month of age, indicating impaired Wnt, FGF, and hedgehog signaling
• accumulation of Sox10+ cells in the apical pulp mesenchyme at 3 months, indicating that nerve-derived mesenchymal stem cells are blocked in their differentiation
• however, immunolocalization of Thy1 (aka, CD90.2, a marker for immune cells and incisor mesenchymal progenitor cells) is normal
|
• enamel epithelium contains cyst-like structures at 3 months; immunohistochemical staining for ameloblastin shows that these epithelial inclusions contain enamel matrix proteins
|
• changes in the periodontal ligament suggest that connective tissue remodeling and continuous incisor eruption are disturbed
|
• width of the lower incisor dentin layer is increased at 1 month of age
|
• incisors show increased dentin formation at 3 months of age
• no phenotype changes are seen in molars
|
• at 3 months, differentiation of odontoblasts in the lower incisors is shifted to the apex
• staining for endogenous alkaline phosphatase confirmed that the signal in the pre-odontoblast layer is shifted to the cervical loop region indicating earlier differentiation
|
• visible enamel defects in the upper incisors at 12 months
• apical enamel layer is fragmented in lower incisors at 6 and 12 months
• a soft food diet restores enamel layer continuity
|
• incisors show increased enamel formation at 3 months of age
• no phenotype changes are seen in molars
|
• at 3 months, differentiation of ameloblasts in the lower incisors is shifted to the apex
|
• enamel mineralization is shifted to the apical part of the incisor in the lower jaw at 6 and 12 months
|
• lower incisor periodontal space is much wider at 6 and 12 months of age; however, the periodontal space of the first molars is unaffected
• a soft food diet does not revert the periodontal defect; a wider periodontal space is still seen in soft diet fed mice at 6 months of age
|
• mice show significant alveolar bone loss around the growing incisor at 6 months of age
• alveolar bone is replaced by a dense scar-like connective tissue, enriched with newly formed nerve fibers likely leading to periodontal pain, decreased food intake and reduced body weight
• a soft food diet does not revert the alveolar bone loss
|
• defects in the periodontal ligament of the growing incisor at 6 months; a thick nerve fiber network is found within the periodontal ligament
• increased nerve branching in the periodontal ligament is likely leading to periodontal pain
• a soft food diet does not ameliorate the presence of branched nerve fibers, indicating that the periodontal ligament defect is the primary cause of the incisor eruption phenotype
|
• both sexes exhibit significantly reduced body weight at 12 months of age
|
weight loss
(
J:302206
)
• aged mice fed a hard pellet diet exhibit weight loss
• using a soft food to reduce mechanical load on the incisor decreases the weight loss observed in aged mice
|
behavior/neurological
• mice fed a hard pellet diet exhibit reduced food intake
|
craniofacial
• lower incisor pulp is completely obliterated at 6 and 12 months of age; blood vessels and nerve fibers disappear in the distal pulp and there is major loss in cellularity
|
• mice show flattening of the lower incisor tips at 6 and 12 months, but not at 1 month of age, suggesting a defect in abrasion and self-sharpening and/or altered occlusion
• micro-computed tomography of the lower incisors at the height of the first molar showed that the width of the dentin layer is increased at 1 month while incisor pulp is completely obliterated and periodontal space is wider at 6 and 12 months
• severe epithelial and mesenchymal differentiation defects are seen in the apical region of the lower incisors at 3 months
• a soft food diet ameliorates both epithelial and mesenchymal differentiation in the incisor apical region
|
• visible enamel defects in the upper incisors at 12 months of age, with only few enamel spots remaining
|
• in situ hybridization analysis revealed reduced expression of Axin2, Fgf10, and Gli1 in the region of the mesenchymal stem cell niche of the incisors at 1 month of age, indicating impaired Wnt, FGF, and hedgehog signaling
• accumulation of Sox10+ cells in the apical pulp mesenchyme at 3 months, indicating that nerve-derived mesenchymal stem cells are blocked in their differentiation
• however, immunolocalization of Thy1 (aka, CD90.2, a marker for immune cells and incisor mesenchymal progenitor cells) is normal
|
• enamel epithelium contains cyst-like structures at 3 months; immunohistochemical staining for ameloblastin shows that these epithelial inclusions contain enamel matrix proteins
|
• changes in the periodontal ligament suggest that connective tissue remodeling and continuous incisor eruption are disturbed
|
• width of the lower incisor dentin layer is increased at 1 month of age
|
• incisors show increased dentin formation at 3 months of age
• no phenotype changes are seen in molars
|
• at 3 months, differentiation of odontoblasts in the lower incisors is shifted to the apex
• staining for endogenous alkaline phosphatase confirmed that the signal in the pre-odontoblast layer is shifted to the cervical loop region indicating earlier differentiation
|
• visible enamel defects in the upper incisors at 12 months
• apical enamel layer is fragmented in lower incisors at 6 and 12 months
• a soft food diet restores enamel layer continuity
|
• incisors show increased enamel formation at 3 months of age
• no phenotype changes are seen in molars
|
• at 3 months, differentiation of ameloblasts in the lower incisors is shifted to the apex
|
• enamel mineralization is shifted to the apical part of the incisor in the lower jaw at 6 and 12 months
|
• at 12 months of age, the mandibular bone is fenestrated in the area of the apical region of the incisor
|
• lower incisor periodontal space is much wider at 6 and 12 months of age; however, the periodontal space of the first molars is unaffected
• a soft food diet does not revert the periodontal defect; a wider periodontal space is still seen in soft diet fed mice at 6 months of age
|
• mice show significant alveolar bone loss around the growing incisor at 6 months of age
• alveolar bone is replaced by a dense scar-like connective tissue, enriched with newly formed nerve fibers likely leading to periodontal pain, decreased food intake and reduced body weight
• a soft food diet does not revert the alveolar bone loss
|
• defects in the periodontal ligament of the growing incisor at 6 months; a thick nerve fiber network is found within the periodontal ligament
• increased nerve branching in the periodontal ligament is likely leading to periodontal pain
• a soft food diet does not ameliorate the presence of branched nerve fibers, indicating that the periodontal ligament defect is the primary cause of the incisor eruption phenotype
|
homeostasis/metabolism
• increased alkaline phosphatase activity in differentiating odontoblasts at 12 months of age
|
skeleton
• mice show significant alveolar bone loss around the growing incisor at 6 months of age
• alveolar bone is replaced by a dense scar-like connective tissue, enriched with newly formed nerve fibers likely leading to periodontal pain, decreased food intake and reduced body weight
• a soft food diet does not revert the alveolar bone loss
|
• lower incisor pulp is completely obliterated at 6 and 12 months of age; blood vessels and nerve fibers disappear in the distal pulp and there is major loss in cellularity
|
• mice show flattening of the lower incisor tips at 6 and 12 months, but not at 1 month of age, suggesting a defect in abrasion and self-sharpening and/or altered occlusion
• micro-computed tomography of the lower incisors at the height of the first molar showed that the width of the dentin layer is increased at 1 month while incisor pulp is completely obliterated and periodontal space is wider at 6 and 12 months
• severe epithelial and mesenchymal differentiation defects are seen in the apical region of the lower incisors at 3 months
• a soft food diet ameliorates both epithelial and mesenchymal differentiation in the incisor apical region
|
• visible enamel defects in the upper incisors at 12 months of age, with only few enamel spots remaining
|
• defects in the periodontal ligament of the growing incisor at 6 months; a thick nerve fiber network is found within the periodontal ligament
• increased nerve branching in the periodontal ligament is likely leading to periodontal pain
• a soft food diet does not ameliorate the presence of branched nerve fibers, indicating that the periodontal ligament defect is the primary cause of the incisor eruption phenotype
|
• in situ hybridization analysis revealed reduced expression of Axin2, Fgf10, and Gli1 in the region of the mesenchymal stem cell niche of the incisors at 1 month of age, indicating impaired Wnt, FGF, and hedgehog signaling
• accumulation of Sox10+ cells in the apical pulp mesenchyme at 3 months, indicating that nerve-derived mesenchymal stem cells are blocked in their differentiation
• however, immunolocalization of Thy1 (aka, CD90.2, a marker for immune cells and incisor mesenchymal progenitor cells) is normal
|
• enamel epithelium contains cyst-like structures at 3 months; immunohistochemical staining for ameloblastin shows that these epithelial inclusions contain enamel matrix proteins
|
• changes in the periodontal ligament suggest that connective tissue remodeling and continuous incisor eruption are disturbed
|
• width of the lower incisor dentin layer is increased at 1 month of age
|
• incisors show increased dentin formation at 3 months of age
• no phenotype changes are seen in molars
|
• at 3 months, differentiation of odontoblasts in the lower incisors is shifted to the apex
• staining for endogenous alkaline phosphatase confirmed that the signal in the pre-odontoblast layer is shifted to the cervical loop region indicating earlier differentiation
|
• visible enamel defects in the upper incisors at 12 months
• apical enamel layer is fragmented in lower incisors at 6 and 12 months
• a soft food diet restores enamel layer continuity
|
• incisors show increased enamel formation at 3 months of age
• no phenotype changes are seen in molars
|
• at 3 months, differentiation of ameloblasts in the lower incisors is shifted to the apex
|
• enamel mineralization is shifted to the apical part of the incisor in the lower jaw at 6 and 12 months
|
• at 12 months of age, the mandibular bone is fenestrated in the area of the apical region of the incisor
|
adipose tissue
• mice fed with hard food diet have significantly less epigonadal white adipose tissue than wild-type controls
• a soft food diet restores the amount of epigonadal white adipose tissue to normal levels
|