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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tnntm1b(KOMP)Wtsi
targeted mutation 1b, Wellcome Trust Sanger Institute
MGI:6507894
Summary 2 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Tnntm1b(KOMP)Wtsi/Tnntm1b(KOMP)Wtsi B6N(Cg)-Tnntm1b(KOMP)Wtsi MGI:6694843
cn2
Gli1tm3(cre/ERT2)Alj/Gli1+
Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/Gt(ROSA)26Sor+
Tnntm1b(KOMP)Wtsi/Tnntm1b(KOMP)Wtsi
involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6N MGI:6694853


Genotype
MGI:6694843
hm1
Allelic
Composition
Tnntm1b(KOMP)Wtsi/Tnntm1b(KOMP)Wtsi
Genetic
Background
B6N(Cg)-Tnntm1b(KOMP)Wtsi
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tnntm1b(KOMP)Wtsi mutation (0 available); any Tnn mutation (91 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
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
• 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




Genotype
MGI:6694853
cn2
Allelic
Composition
Gli1tm3(cre/ERT2)Alj/Gli1+
Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/Gt(ROSA)26Sor+
Tnntm1b(KOMP)Wtsi/Tnntm1b(KOMP)Wtsi
Genetic
Background
involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gli1tm3(cre/ERT2)Alj mutation (2 available); any Gli1 mutation (49 available)
Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo mutation (10 available); any Gt(ROSA)26Sor mutation (993 available)
Tnntm1b(KOMP)Wtsi mutation (0 available); any Tnn mutation (91 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
craniofacial
• after tamoxifen injection, lineage tracing experiments revealed differentiation and proliferation defects in the incisor stem cell compartment at 3 months of age
• GFP+ Gli1 expressing cells are decreased in number and in area in the incisor pulp, indicating decreased hedgehog signaling
• Ki67 immunostaining showed that the proliferation rate of putative mesenchymal stem cells is reduced

growth/size/body
• after tamoxifen injection, lineage tracing experiments revealed differentiation and proliferation defects in the incisor stem cell compartment at 3 months of age
• GFP+ Gli1 expressing cells are decreased in number and in area in the incisor pulp, indicating decreased hedgehog signaling
• Ki67 immunostaining showed that the proliferation rate of putative mesenchymal stem cells is reduced

skeleton
• after tamoxifen injection, lineage tracing experiments revealed differentiation and proliferation defects in the incisor stem cell compartment at 3 months of age
• GFP+ Gli1 expressing cells are decreased in number and in area in the incisor pulp, indicating decreased hedgehog signaling
• Ki67 immunostaining showed that the proliferation rate of putative mesenchymal stem cells is reduced





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last database update
11/12/2024
MGI 6.24
The Jackson Laboratory