Analysis Tools
mortality/aging
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• mice do not survive past 16 days with a mean survival of 10 days
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice do not survive past 16 days with a mean survival of 10 days
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice do not survive past 17 days with a mean survival of 13 days
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• at P5
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• by day 10, mice experience difficulty walking and often fall while walking unlike wild-type mice
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• by day 10, mice experience difficulty walking and often fall while walking unlike wild-type mice
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• at P10, mice exhibit abnormal gait with fibrillation of the hindlimbs
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• in the lumbar region of the spinal cord at P9
• however, spinal motor neuron numbers at P4 are normal
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• at P14, many neuromuscular junctions are partially innervated or not innervated
• the diameter of neuromuscular junctions is smaller than in wild-type mice
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• at P14, muscle fibers of the gastrocnemius are small due to atrophy
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• at P5
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Werdnig-Hoffmann disease | DOID:13137 |
OMIM:253300 |
J:97103 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• average survival of about 2 weeks
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• TH staining of the heart to visualize sympathetic innervation indicates that mutants exhibit fewer major neuronal branches and they appear thinner and less distinct
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• mice preferentially lack innervation of the caudal band of the levator auris longus
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• many endplates are partially occupied or vacant unlike in wild-type mice
• mice exhibit both post- and pre-synaptic pathology at motor neuron endplates
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• muscle fiber diameter is decreased in both slow- and fast-twitch muscles compared to in wild-type mice
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• hearts appear flaccid and lack defined shape and gross attenuation of walls at P10 and P13
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• echocardiography indicates that P6 mice exhibit deficiencies in blood flow out of the right ventricle at the pulmonary valve, with decreased peak velocity and peak gradient, indicating a reduction in pumping efficiency and blood flow from the right ventricle to the lungs
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• as mice near end of life, they display a large increase in heart rate variability, ultimately displaying adjacent RR intervals that are highly inconsistent
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• mice present bradycardia as early as 2 days of age, before neuromuscular symptoms
• bradyarrhythmia is characterized by progressive heart block and reduced ventricular depolarization efficiency
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• at P4, mice have a first-degree heart block characterized by elongated PR interval durations
• at P10, sharp increase in the PR interval and breakdown of cardiac rhythm as mutants exhibit progressive heart block
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• elongation of the time of ventricular depolarization through an increase in QRS interval duration beginning at P4
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• begin to lose weight at around P10
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Werdnig-Hoffmann disease | DOID:13137 |
OMIM:253300 |
J:164446 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mean lifespan is 13 days
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• mutants exhibit an increase in cardiac fibrosis compared to unaffected wild-type controls
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• mutants exhibit an increase in cardiac fibrosis compared to unaffected wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• thinner arterial wall
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• the interventricular septum is partially flattened at P5 and P9
• the interventricular septum lacks the normal curvature which results in a D-shaped left ventricle
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• reduction in width of the interventricular septum at P5 and P9, but not at P2
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• enlargement of the left ventricle at P5 and P9
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• interstitial fibrosis due to oxidative stress is initiated at P2 and progresses rapidly
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• electrocardiogram indicates longer R-R intervals
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• interstitial fibrosis due to oxidative stress is initiated at P2 and progresses rapidly
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• marker analysis indicates oxidative stress in the heart
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Werdnig-Hoffmann disease | DOID:13137 |
OMIM:253300 |
J:164444 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• only one mouse treated with doxycycline at P2 survived for 151 days
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• un-induced mice die on average at P14
• however, mice treated with doxycycline at E13 or at birth live for over 200 days
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• some doxycycline-treated mice exhibit impacted bowel and pockets of fluid and gas unlike control mice
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• doxcycline-treated mice are smaller than control mice
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| N |
• doxycycline-treated mice exhibit normal motor function
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• in doxcycline-treated mice close to death
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• some doxycycline-treated mice exhibit ear necrosis compared with control mice
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| N |
• doxycycline-treated mice exhibit normal endplates and miniature endplate currents and neuromuscular junctions
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/23/2024 MGI 6.23 |
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