Phenotypes Associated with This Genotype

Genotype
MGI:3606141

• Allelic Composition: Enpp1^ttw/Enpp1^ttw
• Genetic Background: involves: ICR

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

mortality/aging

premature death ( J:37369 )

• start to die around 18 weeks of age with most lost before 30 weeks of age

cellular

abnormal chondrocyte proliferation ( J:37369 )

• disorganized proliferation of chondrocytes in the protruded vertebral disks

skeleton

calcified calcaneal tendon ( J:37369 )

• calcification of the Achilles tendon

abnormal axial skeleton morphology ( J:19124 , J:37369 )

• changes are more pronounced and occur earlier in the superior spine than in the inferior spine (J:19124)

• at 8 weeks of age, rigidity of the vertebral column (J:37369)

abnormal vertebrae morphology ( J:19124 , J:43357 )

• proliferation of cartilaginous tissues followed by endochondral ossification occurs around the site of tendon attachment and the around the osseous membrane (J:19124)

• at 10 weeks, proliferation of small fibroblast-like cells is seen at the site of ligament attachment and the posterior corner of the endplate (J:43357)

osteoporosis ( J:37369 )

• moderate

abnormal chondrocyte morphology ( J:19124 )

• at 6 - 8 weeks , degeneration and necrosis of the chondrocytes with surrounding tidemarks of calcification are seen in the articular cartilage

abnormal enthesis morphology ( J:43357 )

• treatment with streptozotocin increased membranous and enchondral ossification of the posterior longitudinal ligament of the cervical spine, esp. in the area of the ligamentous enthesis

• treatment with streptozotocin also increased the number of alkaline phosphatase positive osteoblast-like mesenchymal cells esp. around the enthesis

abnormal joint morphology ( J:19124 , J:37369 )

• at 3 - 4 weeks, papillary proliferation of synovial cells protrude into the articular space (J:19124)

• at 6 - 8 weeks, cystic dilation of the articular sac, proliferation of synovial cells replacing articular cartilage, and some thicker collagen fibers with a longer periodicity are seen (J:19124)

• at 8 - 12 weeks, fibrosis of the synovial tissue is seen, proliferation is not as obvious, and the articular sac is fibrous and thickened with calcification and proliferation of the cartilaginous tissue (J:19124)

• around the site of tendon attachment osteophytes develop and after 20 weeks of age these may bridge the joint (J:19124)

• at 8 weeks of age, stiffness of limb joints (J:37369)

abnormal intervertebral disk morphology ( J:19124 , J:37369 , J:43357 )

• initially at 4 weeks of age, an amorphous calcifying lesion is detected protruding from the cartilaginous endplates into the fibrocartilage in the superior and inferior spine (J:19124)

• this lesion increases in size with age and degenerating or necrotic chondrocytes are seen around the lesion (J:19124)

• abnormal disks protrude into the spinal canaliculi or surrounding soft tissue and are associated with thickening of the osseous membranes and bone formation outside the degenerated calcified fibrous cartilage (J:19124)

• degeneration and destruction of the cartilage matrix with lateral protrusion (J:37369)

• disorganized proliferation of chondrocytes and irregular calcification in the protruded vertebral disks (J:37369)

• progressive dorsal and posterior protrusion of amorphous cartilaginous tissue from the posterior part of the intervertebral disk (J:43357)

• osteoblast-like cells are detected in the posterior intervertebral disks and the membrane surrounding the amorphous protruding tissue is progressively ossified (J:43357)

calcified intervertebral disk ( J:37369 )

• calcified deposits can connect adjacent vertebral bodies similar to spur formation in osteoarthritis

• proliferation of fibrous tissue of the periosteum in areas over protruding intervertebral disks

• deposition of calcium in the intervertebral spaces especially at the edges of the vertebral bodies

calcified joint ( J:19124 , J:37369 )

• at 4 weeks of age calcium deposits begin to accumulate (J:19124)

• at 6 - 8 weeks, calcium deposits are seen in the articular space and synovial tissue by 20 weeks of age the peripheral articular cartilage is replaced by bony tissue (J:19124)

• by 20 weeks of age the peripheral articular cartilage is replaced by bony tissue (J:19124)

• no pronounced deposition of calcium is seen in the kidneys (J:19124)

• in limb joints (J:37369)

abnormal ligament morphology ( J:19124 )

• fibrous thickening of the ligaments around protruding intervertebral disks

abnormal posterior longitudinal ligament morphology ( J:43357 )

• hypertrophy of the posterior longitudinal ligament in the cervical spine at 8 weeks of age

• at 10 weeks, proliferation of small fibroblast-like cells is seen at the site of ligament attachment in the spine

• osteoblast-like cells are detected in the posterior longitudinal ligament

• treatment with streptozotocin increases the area of ossification of the posterior longitudinal ligament

abnormal skeleton physiology ( J:43357 )

abnormal chondrocyte proliferation ( J:37369 )

• disorganized proliferation of chondrocytes in the protruded vertebral disks

osteoarthritis ( J:19124 , J:37369 )

• erosion and destruction of limb joint articular cartilage with synovial cell proliferation but only occasional inflammation (J:37369)

• subchondral bone absorption beneath the joint surface (J:37369)

abnormal bone mineralization ( J:37369 , J:43357 )

• deposition of calcium in the intervertebral spaces especially at the edges of the vertebral bodies (J:37369)

• irregular calcium deposits in areas over protruding intervertebral disks (J:37369)

• ossification of the membrane surrounding the abnormal amorphous tissue of the ligament enthesis (J:43357)

growth/size/body

decreased body weight ( J:43357 )

• streptozotocin-treated mice do not show any increase in body weight compared to to untreated mice unlike in wild-type mice

postnatal growth retardation ( J:37369 )

• at 8 weeks of age, cease to gain weight

behavior/neurological

abnormal grip strength ( J:19124 )

• impaired grasping ability at 3 - 4 weeks of age

abnormal gait ( J:37369 )

• by 8 weeks of age mice appear to walk on tiptoes

cardiovascular system

calcified aorta ( J:37369 )

• calcification of the aorta

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:19124 )

N • serum calcium and phosphorus levels are similar to wild-type

decreased circulating phosphate level ( J:43357 )

calcinosis ( J:37369 )

• calcification of the hair follicles of the vibrissae, aorta, Achilles tendon, and limb joints

increased alkaline phosphatase activity ( J:43357 )

• serum alkaline phosphatase activity is increased at all ages tested and increases rather than decreases with age

immune system

osteoarthritis ( J:19124 , J:37369 )

• erosion and destruction of limb joint articular cartilage with synovial cell proliferation but only occasional inflammation (J:37369)

• subchondral bone absorption beneath the joint surface (J:37369)

muscle

calcified calcaneal tendon ( J:37369 )

• calcification of the Achilles tendon

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ossification of the posterior longitudinal ligament of spine		DOID:0060887	OMIM:602475	J:43357 , J:48527
osteoarthritis		DOID:8398		J:19124 , J:37369
spondyloarthropathy		DOID:1123		J:37369