mortality/aging
• more than 64% of mice die before 12 weeks of age
• the oldest living mouse was 49 weeks old
|
• fewer than the expected numbers of homozygotes are obtained (20% versus expected 25%) from heterozygous breeding
• however, no gross embryonic (E9.5, E12.5) or fetal (E14.5-E18.5) malformations are seen
|
growth/size/body
• increase in volume in the frontal bone with an anterior projection, mimicking the frontal bossing of the human phenotype
|
• incisors or 8-week-old mice have a chalky white color compared to darker yellow/orange pigmentation in wild-type incisors
|
• enamel pigmentation of the labial surface of the incisor is a chalky white instead of being the normal yellow/orange
• the white patches show fragmentation or chipping more pronounced at the bases of the lower incisors
• molars are abraded with enamel loss on the occlusal side exposing the dentin
|
• adult mice show clear amelogenesis imperfecta-like tooth defects
• mice show defective incisor acidification; enamel of 12-week-old mice shows no acid -bands, staining all the enamel yellow, showing no changes in pH during amelogenesis
• enamel is less mature
|
• an overall reduction in optical density is seen in both incisors and molars, indicating reduced enamel mineral density
• teeth show a near complete absence of opaque mineralized enamel matrix
• the enamel matrix has a reduced mineral content
• calcium levels in maturation stage and fully mineralized stage enamel are reduced by more than 80% and 70%, respectively
• phosphorous levels are diminished, with approximately 80% in maturation stage and 50% in fully mineralized stage enamel
• carbon levels, indicative of organic content, are higher in enamel and do not differ between maturation stage and mineralized enamel, suggesting a lack of enamel matrix degradation during the maturation stage of amelogenesis
|
• decrease in dimensions in the nasal bone
|
• mice show significant growth and weight reduction after weaning
|
behavior/neurological
• mice exhibit increased susceptibility to pentylenetetrazol (PTZ)-induced epilepsy and faster seizure onset; mice develop myoclonic seizures as well as clonic seizures which are not seen in the controls
• at the end of the convulsion, more than 90% of mutants present tonic seizures compared to less than 40% of wild-type mice
• however, no spontaneous seizures are seen
|
• mice exhibit memory impairment in the novel object recognition test, showing decreased recognition index with no difference from chance
|
• object exploration time is increased during the acquisition session of the novel object recognition test probably due to hyperactivity
|
|
• muscle strength is decreased in a group of females
• however, mice show no variation in the muscle/body weight ratio and no morphological differences in muscle
|
• mice show increased in locomotor activity during the first hour of the circadian activity test and during habituation, acquisition, and retention sessions of the novel object recognition test, indicating hyperactivity
• however, mice show no differences on the rotarod test indicating no motor impairment and no differences in the elevated plus maze
|
craniofacial
• increase in volume in the frontal bone with an anterior projection, mimicking the frontal bossing of the human phenotype
|
• decrease in dimensions in the occipital bone
|
• increase in volume in the parietal bones with a wider width, mimicking the parietal
bossing of the human phenotype
|
• decrease in dimensions in the temporal bone (with the squamous portion)
|
• incisors or 8-week-old mice have a chalky white color compared to darker yellow/orange pigmentation in wild-type incisors
|
• enamel pigmentation of the labial surface of the incisor is a chalky white instead of being the normal yellow/orange
• the white patches show fragmentation or chipping more pronounced at the bases of the lower incisors
• molars are abraded with enamel loss on the occlusal side exposing the dentin
|
• adult mice show clear amelogenesis imperfecta-like tooth defects
• mice show defective incisor acidification; enamel of 12-week-old mice shows no acid -bands, staining all the enamel yellow, showing no changes in pH during amelogenesis
• enamel is less mature
|
• an overall reduction in optical density is seen in both incisors and molars, indicating reduced enamel mineral density
• teeth show a near complete absence of opaque mineralized enamel matrix
• the enamel matrix has a reduced mineral content
• calcium levels in maturation stage and fully mineralized stage enamel are reduced by more than 80% and 70%, respectively
• phosphorous levels are diminished, with approximately 80% in maturation stage and 50% in fully mineralized stage enamel
• carbon levels, indicative of organic content, are higher in enamel and do not differ between maturation stage and mineralized enamel, suggesting a lack of enamel matrix degradation during the maturation stage of amelogenesis
|
• decrease in dimensions in the premaxillary bone
|
• decrease in dimensions in the maxillary bone
|
• decrease in dimensions in the nasal bone
|
digestive/alimentary system
• 80% of mice show distended stomach full of undigested food
|
• stomach content pH is 6 instead of the normal pH of 3
• however, bowel appears normal with fecal matter present throughout
|
homeostasis/metabolism
|
• males show lower plasma calcium level
|
|
• females show higher levels of plasma alkaline phosphatase
|
nervous system
• mice exhibit increased susceptibility to pentylenetetrazol (PTZ)-induced epilepsy and faster seizure onset; mice develop myoclonic seizures as well as clonic seizures which are not seen in the controls
• at the end of the convulsion, more than 90% of mutants present tonic seizures compared to less than 40% of wild-type mice
• however, no spontaneous seizures are seen
|
• P15 cerebellum shows increased thickness of the external granule layer
|
• the granular layer of the dentate gyrus is thicker at P15
|
• the thickness of the Oriens layer of the CA1 region of the hippocampus is decreased
|
• P15 cerebellum shows increased external granular layer thickness of the simplex lobule
• P15 cerebellum shows decreased thickness of the simplex molecular layer
|
• P15 cerebellum shows increased external granule layer thickness of the paramedian lobule
• however, the vermal lobule IV/V and crus I lobule appear normal
|
• P15 cerebellum shows decreased thickness of the crus II internal granular layer
|
• P15 cerebellum shows decreased thickness of the simplex molecular layer
|
respiratory system
• decrease in dimensions in the nasal bone
|
skeleton
• increase in volume in the frontal bone with an anterior projection, mimicking the frontal bossing of the human phenotype
|
• decrease in dimensions in the occipital bone
|
• increase in volume in the parietal bones with a wider width, mimicking the parietal
bossing of the human phenotype
|
• decrease in dimensions in the temporal bone (with the squamous portion)
|
• incisors or 8-week-old mice have a chalky white color compared to darker yellow/orange pigmentation in wild-type incisors
|
• enamel pigmentation of the labial surface of the incisor is a chalky white instead of being the normal yellow/orange
• the white patches show fragmentation or chipping more pronounced at the bases of the lower incisors
• molars are abraded with enamel loss on the occlusal side exposing the dentin
|
• adult mice show clear amelogenesis imperfecta-like tooth defects
• mice show defective incisor acidification; enamel of 12-week-old mice shows no acid -bands, staining all the enamel yellow, showing no changes in pH during amelogenesis
• enamel is less mature
|
• an overall reduction in optical density is seen in both incisors and molars, indicating reduced enamel mineral density
• teeth show a near complete absence of opaque mineralized enamel matrix
• the enamel matrix has a reduced mineral content
• calcium levels in maturation stage and fully mineralized stage enamel are reduced by more than 80% and 70%, respectively
• phosphorous levels are diminished, with approximately 80% in maturation stage and 50% in fully mineralized stage enamel
• carbon levels, indicative of organic content, are higher in enamel and do not differ between maturation stage and mineralized enamel, suggesting a lack of enamel matrix degradation during the maturation stage of amelogenesis
|
• decrease in dimensions in the premaxillary bone
|
• decrease in dimensions in the maxillary bone
|
• decrease in dimensions in the nasal bone
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
Kohlschutter-Tonz syndrome | DOID:0111668 |
OMIM:226750 |
J:344072 |