Phenotypes associated with this allele

• Allele Symbol: Dmp1^tm1Mis
• Allele Name: targeted mutation 1, Yuji Mishina
• Allele ID: MGI:3040629
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dmp1^tm1Mis/Dmp1^tm1Mis	involves: 129S7/SvEvBrd	MGI:3795595
hm2	Dmp1^tm1Mis/Dmp1^tm1Mis	involves: 129S7/SvEvBrd * C57BL/6	MGI:3041399
hm3	Dmp1^tm1Mis/Dmp1^tm1Mis	involves: 129S7/SvEvBrd * CD-1	MGI:5694692
ht4	Dmp1^tm1Mis/Dmp1^tm1.1Mis	involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6 * CBA	MGI:3795596

Genotype
MGI:3795595

hm1

• Allelic Composition: Dmp1^tm1Mis/Dmp1^tm1Mis
• Genetic Background: involves: 129S7/SvEvBrd

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

skeleton

short femur ( J:135314 )

abnormal long bone metaphysis morphology ( J:135314 )

• expanded

abnormal compact bone morphology ( J:135314 )

• maturation of woven bone is defective

delayed bone ossification ( J:135314 )

• secondary ossification is delayed

limbs/digits/tail

short femur ( J:135314 )

Genotype
MGI:3041399

hm2

• Allelic Composition: Dmp1^tm1Mis/Dmp1^tm1Mis
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

Abnormal tooth morphology and mineralization in Dmp1^tm1Mis/Dmp1^tm1Mis pups

craniofacial

abnormal dental pulp cavity morphology ( J:89498 )

• upper first molars show enlarged pulp chambers and root canals by 1 month of age

decreased molar number ( J:89498 )

• the third molar is either absent or retarded in about 10% of mice

abnormal tooth mineralization ( J:89498 )

• teeth show reduced mineral content after 3 days of age

abnormal cementum mineralization ( J:241769 )

• cementum is malformed and shows defective mineralization with immature calcospherites

growth retardation of molars ( J:89498 )

• delayed development of the third molar in about 10% of mice

abnormal dentin morphology ( J:89498 , J:241769 )

• dentin layer is reduced at 3 days of age (J:89498)

• upper first molars show reduced dentin root thickness by 1 month of age and a dramatic change of dentin matrix structure at 3 months of age (J:89498)

• upper first molars show a poorly organized dentin peritubular ultrastructure with increased spaces and a coarse and irregular dentin surface at 3 months of age (J:89498)

• dentin zone is decreased in 1- and 12-month upper first molars and 3-month incisors (J:89498)

• signs of dentin defects (enlarged pulp and thin dentin) are obvious at 3 weeks of age (J:241769)

abnormal dentin development ( J:89498 )

• both incisors and molars show partial failure of maturation of predentin into dentin during postnatal development

abnormal dentin mineralization ( J:89498 )

• upper first molars show a progressive reduction in root dentin thickness and mineral density after 3 weeks, with a severe decrease in mineralization at 3 months of age

abnormal predentin morphology ( J:89498 )

• predentin layer is reduced at 3 days of age

• width of predentin zone is expanded in 1- and 12-month upper first molars and 3-month incisors

reduced enamel thickness ( J:89498 )

• enamel layer is reduced at 3 days of age

• enamel layer is thinner in 1- and 12-month upper first molars and 3-month incisors

misaligned teeth ( J:241769 )

• misalignment of teeth due to severe alveolar bone loss

abnormal periodontium morphology ( J:241769 )

• mice develop an early-onset periodontal breakdown, with a severe alveolar bone defect and periodontal ligament (PDL)/cementum detachment at 3 and 6 months of age

• periodontal breakdown worsens with age, esp. in the interproximal area between molars

abnormal alveolar process morphology ( J:89498 , J:241769 )

• mineral content of alveolar bone appears to be increased at 3 days of age (J:89498)

• alveolar bone appears woven and immature at 3 weeks and 3 months of age, with more osteoblasts and large bone marrow spaces, suggesting impaired maturation of woven bone into lamellar bone (J:241769)

• porous, hypomineralized alveolar bone is evident at 3 and 6 months of age, with extreme porosity seen by 12 months (J:241769)

• dramatic increase in proteoglycans (biglycan and decorin) and defective osteocyte lacuno-canalicular system in alveolar bone at 3 weeks and 3 months of age (J:241769)

alveolar process atrophy ( J:241769 )

• significant decrease of alveolar bone width and alveolar bone area between the first and second molars at 3 months, but not at 3 weeks of age; however, alveolar bone height is normal, suggesting the defect in interproximal bone is mainly vertical

• severe alveolar bone loss by 12 months of age

abnormal periodontal ligament morphology ( J:241769 )

• detachment between the PDL and cementum at 3 months of age

• the PDL layer is composed of fewer and mostly spindle-shaped fibroblasts, unlike in wild-type controls where PDL cells are mixed with few spindle-like shapes

abnormal cementoblast morphology ( J:241769 )

• cementoblasts are fewer in number and no longer cuboid, but spindle-shaped

decreased cementoblast number ( J:241769 )

• cementoblasts are fewer in number

abnormal acellular cementum morphology ( J:241769 )

• the acellular cementum layer is much thinner and more difficult to discern

abnormal cellular cementum morphology ( J:241769 )

• increased expression of biglycan and decorin in cellular cementum at 3 weeks and 3 months of age

abnormal cementocyte lacunocanalicular system morphology ( J:241769 )

abnormal cementocyte dendritic process morphology ( J:241769 )

• fewer cementocyte dendrites

abnormal cementocyte canaliculus morphology ( J:241769 )

• cementocyte canaliculi are reduced in number

abnormal cementocyte lacuna morphology ( J:241769 )

• the cementocyte lacuna is rough on the lacunar wall, with few dendrites

immune system

increased susceptibility to bacterial infection ( J:241769 )

• mice are more prone to bacterial infection upon aging (1 yr); bacterial colonies, infiltrated lymphocytes and neutrophils, and detritus such as hair shafts are present in 12-month-old mandibles, most likely due to alveolar bone loss and PDL detachment

skeleton

skeleton phenotype ( J:85859 )

N • the overall development of the skeleton in mouse fetuses and newborns was grossly normal

abnormal alveolar process morphology ( J:89498 , J:241769 )

• mineral content of alveolar bone appears to be increased at 3 days of age (J:89498)

• alveolar bone appears woven and immature at 3 weeks and 3 months of age, with more osteoblasts and large bone marrow spaces, suggesting impaired maturation of woven bone into lamellar bone (J:241769)

• porous, hypomineralized alveolar bone is evident at 3 and 6 months of age, with extreme porosity seen by 12 months (J:241769)

• dramatic increase in proteoglycans (biglycan and decorin) and defective osteocyte lacuno-canalicular system in alveolar bone at 3 weeks and 3 months of age (J:241769)

alveolar process atrophy ( J:241769 )

• significant decrease of alveolar bone width and alveolar bone area between the first and second molars at 3 months, but not at 3 weeks of age; however, alveolar bone height is normal, suggesting the defect in interproximal bone is mainly vertical

• severe alveolar bone loss by 12 months of age

abnormal dental pulp cavity morphology ( J:89498 )

• upper first molars show enlarged pulp chambers and root canals by 1 month of age

decreased molar number ( J:89498 )

• the third molar is either absent or retarded in about 10% of mice

abnormal periodontal ligament morphology ( J:241769 )

• detachment between the PDL and cementum at 3 months of age

• the PDL layer is composed of fewer and mostly spindle-shaped fibroblasts, unlike in wild-type controls where PDL cells are mixed with few spindle-like shapes

abnormal cementoblast morphology ( J:241769 )

• cementoblasts are fewer in number and no longer cuboid, but spindle-shaped

decreased cementoblast number ( J:241769 )

• cementoblasts are fewer in number

abnormal tooth mineralization ( J:89498 )

• teeth show reduced mineral content after 3 days of age

abnormal cementum mineralization ( J:241769 )

• cementum is malformed and shows defective mineralization with immature calcospherites

growth retardation of molars ( J:89498 )

• delayed development of the third molar in about 10% of mice

abnormal acellular cementum morphology ( J:241769 )

• the acellular cementum layer is much thinner and more difficult to discern

abnormal cellular cementum morphology ( J:241769 )

• increased expression of biglycan and decorin in cellular cementum at 3 weeks and 3 months of age

abnormal cementocyte lacunocanalicular system morphology ( J:241769 )

abnormal cementocyte dendritic process morphology ( J:241769 )

• fewer cementocyte dendrites

abnormal cementocyte canaliculus morphology ( J:241769 )

• cementocyte canaliculi are reduced in number

abnormal cementocyte lacuna morphology ( J:241769 )

• the cementocyte lacuna is rough on the lacunar wall, with few dendrites

abnormal dentin morphology ( J:89498 , J:241769 )

• dentin layer is reduced at 3 days of age (J:89498)

• upper first molars show reduced dentin root thickness by 1 month of age and a dramatic change of dentin matrix structure at 3 months of age (J:89498)

• upper first molars show a poorly organized dentin peritubular ultrastructure with increased spaces and a coarse and irregular dentin surface at 3 months of age (J:89498)

• dentin zone is decreased in 1- and 12-month upper first molars and 3-month incisors (J:89498)

• signs of dentin defects (enlarged pulp and thin dentin) are obvious at 3 weeks of age (J:241769)

abnormal dentin development ( J:89498 )

• both incisors and molars show partial failure of maturation of predentin into dentin during postnatal development

abnormal dentin mineralization ( J:89498 )

• upper first molars show a progressive reduction in root dentin thickness and mineral density after 3 weeks, with a severe decrease in mineralization at 3 months of age

abnormal predentin morphology ( J:89498 )

• predentin layer is reduced at 3 days of age

• width of predentin zone is expanded in 1- and 12-month upper first molars and 3-month incisors

reduced enamel thickness ( J:89498 )

• enamel layer is reduced at 3 days of age

• enamel layer is thinner in 1- and 12-month upper first molars and 3-month incisors

misaligned teeth ( J:241769 )

• misalignment of teeth due to severe alveolar bone loss

abnormal long bone hypertrophic chondrocyte zone ( J:85859 )

• modest expansion of the hypertrophic chondrocyte zone in fetuses at E18

increased diameter of long bones ( J:85859 )

• modest increase in long bone diameter

increased osteoblast cell number ( J:241769 )

• increased numbers of osteoblasts in alveolar bone at 3 weeks and 3 months of age

abnormal osteocyte lacunocanalicular system morphology ( J:241769 )

• disorganized osteocyte lacuno-canalicular system in alveolar bone at 3 weeks and 3 months of age

abnormal osteocyte canaliculus morphology ( J:241769 )

• fewer osteocyte canaliculi with rough canalicular walls in alveolar bone; canaliculi are less straight and smooth

abnormal osteocyte lacuna morphology ( J:241769 )

• osteocyte lacunae have rough walls and are larger in size in alveolar bone; distribution of the lacunae appears less organized and more clustered

increased osteoid volume ( J:241769 )

• increased amount of osteoid present in the matrix in alveolar bone at 3 weeks and 3 months of age

abnormal bone mineralization involved in bone maturation ( J:241769 )

• alveolar bone is woven and immature at 3 weeks and 3 months of age, with more osteoblasts and large bone marrow spaces, suggesting impaired maturation of woven bone into lamellar bone

decreased bone mineralization ( J:241769 )

• porous, hypomineralized alveolar bone is evident at 3 and 6 months of age, with extreme porosity seen by 12 months

growth/size/body

abnormal dental pulp cavity morphology ( J:89498 )

• upper first molars show enlarged pulp chambers and root canals by 1 month of age

decreased molar number ( J:89498 )

• the third molar is either absent or retarded in about 10% of mice

abnormal tooth mineralization ( J:89498 )

• teeth show reduced mineral content after 3 days of age

abnormal cementum mineralization ( J:241769 )

• cementum is malformed and shows defective mineralization with immature calcospherites

growth retardation of molars ( J:89498 )

• delayed development of the third molar in about 10% of mice

abnormal dentin morphology ( J:89498 , J:241769 )

• dentin layer is reduced at 3 days of age (J:89498)

• upper first molars show reduced dentin root thickness by 1 month of age and a dramatic change of dentin matrix structure at 3 months of age (J:89498)

• upper first molars show a poorly organized dentin peritubular ultrastructure with increased spaces and a coarse and irregular dentin surface at 3 months of age (J:89498)

• dentin zone is decreased in 1- and 12-month upper first molars and 3-month incisors (J:89498)

• signs of dentin defects (enlarged pulp and thin dentin) are obvious at 3 weeks of age (J:241769)

abnormal dentin development ( J:89498 )

• both incisors and molars show partial failure of maturation of predentin into dentin during postnatal development

abnormal dentin mineralization ( J:89498 )

• upper first molars show a progressive reduction in root dentin thickness and mineral density after 3 weeks, with a severe decrease in mineralization at 3 months of age

abnormal predentin morphology ( J:89498 )

• predentin layer is reduced at 3 days of age

• width of predentin zone is expanded in 1- and 12-month upper first molars and 3-month incisors

reduced enamel thickness ( J:89498 )

• enamel layer is reduced at 3 days of age

• enamel layer is thinner in 1- and 12-month upper first molars and 3-month incisors

misaligned teeth ( J:241769 )

• misalignment of teeth due to severe alveolar bone loss

abnormal periodontium morphology ( J:241769 )

• mice develop an early-onset periodontal breakdown, with a severe alveolar bone defect and periodontal ligament (PDL)/cementum detachment at 3 and 6 months of age

• periodontal breakdown worsens with age, esp. in the interproximal area between molars

abnormal alveolar process morphology ( J:89498 , J:241769 )

• mineral content of alveolar bone appears to be increased at 3 days of age (J:89498)

• alveolar bone appears woven and immature at 3 weeks and 3 months of age, with more osteoblasts and large bone marrow spaces, suggesting impaired maturation of woven bone into lamellar bone (J:241769)

• porous, hypomineralized alveolar bone is evident at 3 and 6 months of age, with extreme porosity seen by 12 months (J:241769)

• dramatic increase in proteoglycans (biglycan and decorin) and defective osteocyte lacuno-canalicular system in alveolar bone at 3 weeks and 3 months of age (J:241769)

alveolar process atrophy ( J:241769 )

• significant decrease of alveolar bone width and alveolar bone area between the first and second molars at 3 months, but not at 3 weeks of age; however, alveolar bone height is normal, suggesting the defect in interproximal bone is mainly vertical

• severe alveolar bone loss by 12 months of age

abnormal periodontal ligament morphology ( J:241769 )

• detachment between the PDL and cementum at 3 months of age

• the PDL layer is composed of fewer and mostly spindle-shaped fibroblasts, unlike in wild-type controls where PDL cells are mixed with few spindle-like shapes

abnormal cementoblast morphology ( J:241769 )

• cementoblasts are fewer in number and no longer cuboid, but spindle-shaped

decreased cementoblast number ( J:241769 )

• cementoblasts are fewer in number

abnormal acellular cementum morphology ( J:241769 )

• the acellular cementum layer is much thinner and more difficult to discern

abnormal cellular cementum morphology ( J:241769 )

• increased expression of biglycan and decorin in cellular cementum at 3 weeks and 3 months of age

abnormal cementocyte lacunocanalicular system morphology ( J:241769 )

abnormal cementocyte dendritic process morphology ( J:241769 )

• fewer cementocyte dendrites

abnormal cementocyte canaliculus morphology ( J:241769 )

• cementocyte canaliculi are reduced in number

abnormal cementocyte lacuna morphology ( J:241769 )

• the cementocyte lacuna is rough on the lacunar wall, with few dendrites

Genotype
MGI:5694692

hm3

• Allelic Composition: Dmp1^tm1Mis/Dmp1^tm1Mis
• Genetic Background: involves: 129S7/SvEvBrd * CD-1

cardiovascular system

abnormal vascular development ( J:184352 )

• delay in blood vessel formation in bones at E11

• mice injected with anti-Fgf23 antibodies show rescue of the delay

homeostasis/metabolism

increased circulating parathyroid hormone level ( J:115339 )

decreased circulating calcium level ( J:115339 )

• mild hypocalcemia

decreased circulating phosphate level ( J:115339 , J:184352 )

• severe hypophosphatemia (J:115339)

• mice injected with anti-Fgf23 antibodies show restoration of phosphate levels (J:184352)

abnormal circulating protein level ( J:115339 )

• elevation in serum Fgf23 levels

increased alkaline phosphatase activity ( J:184352 )

cellular

arrested osteoblast differentiation ( J:184352 )

• osteoblasts continuously express osteoblast-specific genes and fail to differentiate into mature osteocytes

renal/urinary system

abnormal kidney physiology ( J:115339 )

• increase in renal phosphorous clearance

skeleton

decreased osteoclast cell number ( J:184352 )

• the number of osteoclasts formed in bone marrow cultures in the presence of 1,25-(OH)2D3 is less than 50% of that in control

• marker analysis indicates a reduction in osteoclasts in long bone in both the epiphysis and metaphysis at 2 weeks of age

• however, the number of osteoclasts formed by spleen cells is normal, indicating that osteoclast precursors can differentiate normally

abnormal long bone metaphysis morphology ( J:184352 )

• expansion of the metaphysis

abnormal compact bone morphology ( J:184352 )

• abnormalities in cortical bone

• mice treated with anti-Fgf13 antibodies show improvement in cortical bone abnormalities

abnormal osteocyte lacunocanalicular system morphology ( J:115339 )

• defective organization of osteocyte lacunae and lacunocanalicular walls

• the inner lacunocanalicular wall is buckled and enlarged rather than smooth in the poorly mineralized matrix, unmineralized collagen fibrils are seen, the lamina limitans is absent, and the membrane surface is buckled and irregular

abnormal osteocyte morphology ( J:115339 )

• marker analysis indicates defective osteoblast-to-osteocyte differentiation and osteocyte maturation

abnormal osteocyte lacuna morphology ( J:115339 )

• osteocyte lacunae are larger and randomly oriented

increased bone trabecula number ( J:184352 )

• increase in accumulation of trabecular bone in the bone marrow space

abnormal skeleton development ( J:115339 )

arrested osteoblast differentiation ( J:184352 )

• osteoblasts continuously express osteoblast-specific genes and fail to differentiate into mature osteocytes

rachitic rosary ( J:115339 )

• rachitic rosary of the ribs

osteomalacia ( J:115339 )

• mice exhibit defects in bone mineralization showing diffuse, osteomalacic form of mineralization; develops with age

• mineral content is either missing or sparsely located in regions surrounding osteocytes

• spherical structures reminiscent of calculospherulites are present

rickets ( J:115339 )

• mice develop rickets with age, showing, showing flared ends of long bones and rachitic rosary of the ribs

• high-phosphate diet rescues the rickets but not the osteomalacia

delayed bone ossification ( J:184352 )

• delay in formation of secondary ossification centers that is mainly due to hypophosphatemia

• mice injected with anti-Fgf23 antibodies show rescue of secondary ossification defects in vertebrae and femoral bone

abnormal bone remodeling ( J:184352 )

• cartilage is remodeled less in 3 day old forelimbs than in controls

• mice at 1 year of age show development of large bony protuberances in all bones, suggesting abnormal bone remodeling processes with age

• bone remodeling abnormalities are due to altered osteoblast function and a reduction of the number of osteoclasts

hematopoietic system

decreased osteoclast cell number ( J:184352 )

• the number of osteoclasts formed in bone marrow cultures in the presence of 1,25-(OH)2D3 is less than 50% of that in control

• marker analysis indicates a reduction in osteoclasts in long bone in both the epiphysis and metaphysis at 2 weeks of age

• however, the number of osteoclasts formed by spleen cells is normal, indicating that osteoclast precursors can differentiate normally

immune system

decreased osteoclast cell number ( J:184352 )

• the number of osteoclasts formed in bone marrow cultures in the presence of 1,25-(OH)2D3 is less than 50% of that in control

• marker analysis indicates a reduction in osteoclasts in long bone in both the epiphysis and metaphysis at 2 weeks of age

• however, the number of osteoclasts formed by spleen cells is normal, indicating that osteoclast precursors can differentiate normally

abnormal bone marrow development ( J:184352 )

• delay in bone marrow formation at E11

• mice injected with anti-Fgf23 antibodies show accelerated bone marrow formation in the femur epiphysis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive hypophosphatemic rickets		DOID:0050949	OMIM:241520 OMIM:613312	J:184352

Genotype
MGI:3795596

ht4

• Allelic Composition: Dmp1^tm1Mis/Dmp1^tm1.1Mis
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6 * CBA

skeleton

abnormal long bone metaphysis morphology ( J:135314 )

• expanded

abnormal compact bone morphology ( J:135314 )

• maturation of woven bone is defective

delayed bone ossification ( J:135314 )

• secondary ossification is delayed