Analysis Tools
cellular
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• by 2 weeks of age homozygotes have an excess of goblet cells around the opening of the Eustachian tubes and in the Eustachian tube ducts, this is still seen at 2 months of age, and excessive mucin secretion interferes with ciliary function
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craniofacial
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• the round window membrane is thicker than normal and there is overossification of the reound window ridge
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• fusion of the malleus and incus
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skeleton
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• the round window membrane is thicker than normal and there is overossification of the reound window ridge
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• fusion of the malleus and incus
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• arthritis found in the spine at 12 weeks of age
• osteoarthritis found in many joints and joints are very stiff and unbendable at 7 months of age
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• severe osteomyelitis of the joints and unusual synovial cysts found at 13 weeks of age
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• dilated joint spaces and hyperplastic synovium in the elbows found at 11 weeks of age
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• dilated joint spaces and hyperplastic synovium in the knees found at 11 weeks of age
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• stiffening of the joints is seen by around 2 months of age, particularly the forepaws
• on an 'acceleration diet' rich in phosphorus and low in magnesium, mutants show accelerated stiffening of the joints and hobbling gait
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growth/size/body
hearing/vestibular/ear
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• although abnormalities are not found in the inner ear, all ears with elevated ABR thresholds have middle ear defects such as retracted tympanic membrane, effusion in the middle ear, thickened epithelium with fibrous polyps, and in older mice the excessive accumulation of discharge in the external ear canal
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• the wall of the stapedial artery is thicker than normal with excessive calcium deposition
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• by 2 weeks of age homozygotes have an excess of goblet cells around the opening of the Eustachian tubes and in the Eustachian tube ducts, this is still seen at 2 months of age, and excessive mucin secretion interferes with ciliary function
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• the round window membrane is thicker than normal and there is overossification of the reound window ridge
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• fusion of the malleus and incus
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• amorphous tissue is found in the Eustachian tubes
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• at 8 weeks the middle ear cavity is filled with an aqueous effusion containing amorphous tissue masses, and at 12 weeks it is filled with pus-like secretions and an amorphous tissue mass
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• white patch at pars tensa and retracted tempanic membrane by 6 months of age
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• although no indication of vestibular impairment is found, hearing is impaired with normal hearing at 3 weeks of age, 20-25 db elevations in thresholds occurs by 6 weeks of age, a stable period of little increase in thresholds between 6 and 12 weeks, then a loss of 20-15 db between 12 and 18 weeks of age
• only one of eleven homozygotes have normal ABR thresholds in both ears at 12 weeks of age
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• auditory brainstem response shows moderate to severe hearing loss by 3 months of age
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immune system
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• arthritis found in the spine at 12 weeks of age
• osteoarthritis found in many joints and joints are very stiff and unbendable at 7 months of age
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• severe osteomyelitis of the joints and unusual synovial cysts found at 13 weeks of age
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integument
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• mice from mothers on the acceleration diet during pregnancy exhibit extensive mineralization in the dermal sheath of vibrissae as early as 4 weeks of age and shows progression with age, showing a 17.7-fold increase in mineral content of the muzzle skin containing vibrissae
• on a normal diet, mutants exhibit less mineralization in the dermal sheath of vibrissae
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• mineralization of the capsule of the follicles of the vibrissae is found at 7 months of age
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• mice from mothers on the acceleration diet during pregnancy and fed the same diet exhibit extensive mineralization in the dermal sheath of vibrissae as early as 4 weeks of age which progresses with age
(J:201689)
• severe calcification of the fibrous capsule surrounding the muzzle vibrissae by 15 weeks of age
(J:252837)
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behavior/neurological
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• by 2 months of age homozygotes have a stiff posture with the front legs held in toward the body
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• slow, hobbling gait beginning at around 2 months of age due to joint disease
(J:174912)
• on an 'acceleration diet'rich in phosphorus and low in magnesium, mutants show accelerated stiffening of the joints and hobbling gait
(J:201689)
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cardiovascular system
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• mice from mothers on the acceleration diet during pregnancy and also fed this diet exhibit extensive mineralization in the aorta
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• mice from mothers on the acceleration diet during pregnancy and also fed this diet exhibit extensive mineralization in the carotid arteries
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• mice from mothers on the acceleration diet during pregnancy and also fed this diet exhibit extensive mineralization in the coronary arteries
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• mice from mothers on the acceleration diet during pregnancy and also fed this diet show calcification of the carotid and coronary arteries
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• seen in mice from mothers on the acceleration diet during pregnancy and also fed this diet
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• the wall of the stapedial artery is thicker than normal with excessive calcium deposition
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• mice from mothers on the acceleration diet during pregnancy and also fed this diet exhibit mineralized blood vessels in the liver, but no mineralization in the liver parenchyma
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homeostasis/metabolism
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• at 8 weeks the middle ear cavity is filled with an aqueous effusion containing amorphous tissue masses, and at 12 weeks it is filled with pus-like secretions and an amorphous tissue mass
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• feeding a high phosphorous/low magnesium diet from 4 weeks of age until assessment at 12 weeks of age increases the calcium deposits throughout all of the affected tissues and additionally in the liver but this is less severe than the response to the same treatment in mice homozygous for the ages with stiffened joints 2 Jackson allele, which was assessed on the BALB/cJ backgroud
(J:215824)
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• mice from mothers on the acceleration diet during pregnancy exhibit extensive mineralization in the dermal sheath of vibrissae as early as 4 weeks of age and progresses with age, showing a 17.7-fold increase in mineral content of the muzzle skin containing vibrissae
• at 7 weeks of age, mice on the acceleration diet show severe mineralization in the muzzle area, showing calcium and phosphorus in a 2:1 ratio, similar to that in endochondral bone and the presence of hydroxyapatite
• mice from mothers on the acceleration diet during pregnancy exhibit extensive mineralization in the aorta, the coronary and carotid arteries, the retina, the blood vessels of the liver, and in the kidneys
• on a normal diet, mutants exhibit less mineralization in the dermal sheath of vibrissae
• on a normal diet, vascular mineralization is not seen until around 5 months of age compared to 4 weeks of age on the acceleration diet
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• homozygotes have approximately 20% of normal plasma concentrations of PPi, with concomitant PPi:Pi ratio reduction
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liver/biliary system
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• mice from mothers on the acceleration diet during pregnancy and also fed this diet exhibit mineralized blood vessels in the liver, but no mineralization in the liver parenchyma
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mortality/aging
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• pups from mothers on the acceleration diet during pregnancy and the placed on the same diet at weaning exhibit reduced lifespan, with more than 50% of mice dying spontaneously before the age of 6 weeks and only 4 of 28 mice surviving to 12 weeks of age
• however, mice show normal lifespan on a normal diet
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renal/urinary system
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• mice from mothers on the acceleration diet during pregnancy and also fed this diet exhibit extensive mineralization in the kidneys, affecting primarily the medullary tubules and arcuate and renal arteries
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vision/eye
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• mice from mothers on the acceleration diet during pregnancy and also fed this diet exhibit extensive mineralization in the retina
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• seen in mice from mothers on the acceleration diet during pregnancy and also fed this diet
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limbs/digits/tail
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• dilated joint spaces and hyperplastic synovium in the elbows found at 11 weeks of age
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• dilated joint spaces and hyperplastic synovium in the knees found at 11 weeks of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| arterial calcification of infancy | DOID:0050644 |
OMIM:208000 OMIM:614473 |
J:201689 | |
| otitis media | DOID:10754 | J:251638 | ||
| tympanosclerosis | DOID:1214 | J:251638 | ||
