Analysis Tools
mortality/aging
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• mice exhibit reduced survival ratio (<90%) at 25 weeks with dox treatment
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• mice treated with higher doses of doxycycline (dox) exhibit mortality as early as 2 weeks and 100% mortality rate by 5-6 weeks
• mice treated with a lower dox regiment show 90% mortality rate by 25 weeks after dox treatment initiation
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behavior/neurological
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• mice treated with a combination of 2 mg/ml of doxycycline (dox) in drinking water coupled with 5 of 10 mg/kg intraperitoneal injection beginning at 3 months of age for 20 weeks develop disease phenotypes paralleling those of Friedreich's ataxia; this dox regiment was used for analysis
• mice exhibit reduced hind and front limb stride length at 12 and 24 weeks with dox treatment, indicating ataxic gait
• removal of dox results in rapid improvement in gait ataxia
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• dox treated mice fall faster off the rotarod than controls from 12 weeks onward with dox treatment
• removal of dox results in improvement on the rotarod
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• mice exhibit defects in forelimb muscular strength at 12 and 24 weeks with dox treatment
• removal of dox results in rapid improvement of muscle strength
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• mice exhibit reduced hind and front limb stride length at 12 and 24 weeks with dox treatment
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• dox treated mice exhibit decreased locomotor activity, showing a shorter distance traveled at 12 and 24 weeks with dox treatment
• removal of dox results in improvement in locomotor activity
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cardiovascular system
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• cardiomyocytes show severe disorganization, with disorganized and irregular sarcomeres and enlarged mitochondria at 20 weeks of dox treatment
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• mice exhibit increased myocardial iron at 20 weeks of dox treatment, showing increased ferric iron staining and increased expression of iron metabolic proteins, ferritin and ferroportin
• removal of dox results in reduced iron and ferritin accumulation
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• mice exhibit excessive collagen deposition in hearts at 20 weeks of dox treatment, indicating cardiac fibrosis
• removal of dox results in reduced myocardial fibrosis
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• mice exhibit absence of P-waves at week 24 of dox treatment, suggesting an atrial conduction abnormality
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• mice exhibit an increase in QT interval duration at 12 and 24 weeks post dox treatment
• however, mice exhibit a normal ECG 12 weeks after dox removal
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• mice exhibit ventricular and posterior wall thickening by 24 weeks of dox treatment, indicating hypertrophic cardiomyopathy
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cellular
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• in a minority of mice, cardiomyocytes show mitochondria with disorganized cristae and vacuoles at 20 weeks of dox treatment, suggesting mitochondrial degeneration
• removal of dox results in reduced mitochondrial abnormalities
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• cardiomyocytes have enlarged mitochondria at 20 weeks of dox treatment
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growth/size/body
weight loss
(
J:254962
)
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• mice exhibit weight loss at 25 weeks with dox treatment
• removal of dox results in rapid improvement in body weight
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homeostasis/metabolism
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• mice exhibit increased myocardial iron at 20 weeks of dox treatment, showing increased ferric iron staining and increased expression of iron metabolic proteins, ferritin and ferroportin
• removal of dox results in reduced iron and ferritin accumulation
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• heart shows reduced aconitase, an Fe-S containing enzyme, activity at 20 weeks of dox treatment
• removal of dox results in normal aconitase activity
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muscle
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• cardiomyocytes show severe disorganization, with disorganized and irregular sarcomeres and enlarged mitochondria at 20 weeks of dox treatment
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• mice exhibit ventricular and posterior wall thickening by 24 weeks of dox treatment, indicating hypertrophic cardiomyopathy
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• cardiomyocytes have disorganized and irregular sarcomeres at 20 weeks of dox treatment
• removal of dox results in improved sarcomere organization
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nervous system
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• mice exhibit a decrease in axonal size in the spinal cord at 20 weeks of dox treatment
• however, the number of Purkinje cells and the cerebellar granular and molecular layers are not altered at 20 weeks of dox treatment
• removal of dox results in mild improvement in axonal size in the spinal cord
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• mice exhibit a decrease in myelin sheath thickness in the spinal cord at 20 weeks of dox treatment
• removal of dox results in mild improvement in myelin sheath thickness
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• photoreceptors are disrupted at 20 weeks of dox treatment
• removal of dox results in a reduction of disrupted photoreceptors
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• dorsal root ganglia neurons show an increase in condensed mitochondria at 20 weeks of dox treatment, with most cases showing empty vesicles associated with the condensed mitochondria, suggesting neuronal degeneration
• removal of dox results in fewer condensed, degenerating mitochondria in dorsal root ganglion neurons
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pigmentation
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• mice exhibit an increase in degenerating retinal pigment epithelium cells with vacuoles at 20 weeks of dox treatment
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vision/eye
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• photoreceptors are disrupted at 20 weeks of dox treatment
• removal of dox results in a reduction of disrupted photoreceptors
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• mice exhibit an increase in degenerating retinal pigment epithelium cells with vacuoles at 20 weeks of dox treatment
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Friedreich ataxia | DOID:12705 | J:254962 | ||
