Analysis Tools
growth/size/body
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• slightly reduced growth rate
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homeostasis/metabolism
| N |
• at 3 months of age, urine osmolarity, pH, total urine volume, and urine creatinine, nitrate, potassium, chloride, calcium, and sodium levels are not significantly altered relative to those in wild-type controls
• normal protein and RNA levels of uricase and other enzymes involved in the purine degradation pathway are detected in the liver at 6 months, consistent with normal serum urate levels
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• at 3 months of age, urine uric acid levels are ~10-fold higher than those in wild-type controls
• however, serum uric acid levels are not significantly altered
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• homozygous null fetuses are not affected by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administration which normally causes cleft palate and hydronephrosis
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• altered metabolism of phenobarbital and butylated hydroxyanisole (BHA)
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renal/urinary system
| N |
• no urate stones or histological defects are noted in the kidney at 3 months of age
• urine osmolarity, pH, total urine volume, and urine creatinine, nitrate, potassium, chloride, calcium, and sodium levels are not significantly altered
• normal mRNA levels of several urate transporters are detected in the kidney at 6 months
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• at 3 months of age, urine uric acid levels are ~10-fold higher than those in wild-type controls
• however, serum uric acid levels are not significantly altered
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• at 10 weeks of age, an increased number of F4/80-positive macrophages is detected in the stroma of the urinary bladder relative to controls
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• by 6 months of age, invading epithelial cells are observed in the submucosal and muscle layers of the bladder in some mice indicating malignant changes, unlike in control mice
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• at 4 months of age, homozygotes exhibit more apoptotic (TUNEL+) cells in some areas of the bladder relative to control mice
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• at 10 weeks of age, urinary bladder blood vessels are dilated, unlike in control bladders
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• at 10 weeks of age, the luminal side of the bladder epithelium is filled with numerous eosinophilic granules that stain positive for methenamine silver (a uric acid marker), unlike in control bladders
• after treatment with uricase and hydrogen peroxide, these granules are no longer present in the epithelium
• loss of E-cadherin is noted in some disorganized areas of the urothelium, unlike in control mice
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• at 10 weeks of age, tiny uric acid stones of a rough and pitted appearance are first noted in some mice
• by 6 months of age, all homozygotes exhibit 2-3 uric acid stones ~3-4 mm in diameter in the urinary bladder
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• at 10 weeks of age, a thicker collagen layer and increased fibrosis are noted in the submucosal layer of the urinary bladder; more severe at 6 months
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neoplasm
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• by 6 months of age, invading epithelial cells are observed in the submucosal and muscle layers of the bladder in some mice indicating malignant changes, unlike in control mice
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immune system
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• at 10 weeks of age, an increased number of F4/80-positive macrophages is detected in the stroma of the urinary bladder relative to controls
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cardiovascular system
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• at 10 weeks of age, urinary bladder blood vessels are dilated, unlike in control bladders
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skeleton
| N |
• no histological abnormalities are noted in the joints at 3 months of age
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behavior/neurological
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• the optokinetic reflex is decreased as indicated by a decrease in the dominant eye velocity when eye movements are evoked in horizontal position during a rotation at 5 degrees/second in light in counter-clockwise
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• the gaze of mutants is unstable at rest
• ocular instability affects both eyes, is observed in both dark and light, and consists of rhythmic sinusoidal, purely horizontal eye movements, indicating horizontal pendular nystagmus
• frequency of the ocular instability varies from 0.5 to 5 Hz and frequency of the nystagmus in the light is higher
• the nystagmus evolves throughout the lifespan from pendular nystagmus to jerk nystagmus
• nystagmus impairs gaze stabilization as long as the head movement is of mild intensity, however, the vestibular stimulation triggered by head movements of higher intensity leads to normal compensatory eye movement and proper gaze stabilization, indicating that the nystagmus is not purely of vestibular origin
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hearing/vestibular/ear
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• the gaze of mutants is unstable at rest
• ocular instability affects both eyes, is observed in both dark and light, and consists of rhythmic sinusoidal, purely horizontal eye movements, indicating horizontal pendular nystagmus
• frequency of the ocular instability varies from 0.5 to 5 Hz and frequency of the nystagmus in the light is higher
• the nystagmus evolves throughout the lifespan from pendular nystagmus to jerk nystagmus
• nystagmus impairs gaze stabilization as long as the head movement is of mild intensity, however, the vestibular stimulation triggered by head movements of higher intensity leads to normal compensatory eye movement and proper gaze stabilization, indicating that the nystagmus is not purely of vestibular origin
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nervous system
| N |
• cerebellum exhibits a normal structure and function (mutants are capable of adaptation during and after the vestibulo-ocular conflict)
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vision/eye
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• retina of some mutants shows disorganization of the synapses between the bipolar cells and the retinal ganglion cells; projections of the bipolar neurons onto the retinal ganglion cell dendrites are not lamina-restricted as in wild-type mice and are scattered with the synaptic boutons of the bipolar cells disseminated throughout the inner plexiform layer of the retina
• however, electroretinograms show normal retinal function
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| congenital nystagmus | DOID:9649 |
OMIM:PS310700 |
J:195817 | |
