Analysis Tools
mortality/aging
premature death
(
J:165
)
|
• very reduced viability
|
growth/size/body
|
• atrophy of facial muscle gives a pointed appearance to the snout and results in the ears being laid back
|
upturned snout
(
J:6388
)
|
• upward pointed snout
|
|
• at 30 days of age
(J:1563)
• 47% normal
(J:1563)
|
behavior/neurological
|
• unusual clasping of feet when suspended by tail
(J:6388)
|
|
• in forepaws
• muscle weakness by fourth or fifth week
|
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• head and anterior trunk held lower than normal
|
|
• by 30 days of age
(J:1563)
• high stepping and unsteady
(J:5102)
• eventually walk on dorsum of forepaws due to the inability to extend the paws at the wrist
(J:5102)
• ultimately they push the body along using their hind legs only
(J:5102)
|
|
• paralysis primarily affects forelimbs
(J:165)
• clasping of front paws and difficulties using front legs
(J:1563)
|
nervous system
|
• brain stem and spinal cord through the thoracic region weighs 62-68% of controls
• cross section area of spinal cord 75-80% of normal
|
|
• small numbers of GFAP positive cells in the anterior horn of the spinal cord at 1 month of age and found throughout the gray matter by 10 months
• astrocyte processes perpendicular to surface of cord rather than parallel as in controls
• GFAP reactive material gradually increases from 2 to 5 months of age
|
|
• eccentric nuclei
(J:5102)
• enlarged soma
(J:19087)
• poorly stained Nissl bodies
(J:19087)
• reduced numbers of dendrites
(J:19087)
|
|
• in brain stem and spinal cord but not basal ganglia or cerebral cortex
(J:5102)
• progressive denervation of skeletal muscle
(J:5102)
• sprouting from myelinated part of preterminal axons and nerve fibers innervate several muscle fibers
(J:5102)
• reduced numbers of motor nerves in affected muscle
(J:5102)
• vacuolated neurons develop in the cervical spinal cord with much larger surface areas in x-section and smaller nuclear areas
(J:6238)
• normal neurons are smaller in x-section but with normal nuclear areas
(J:6238)
• protein synthesis reduced in both types of neurons
(J:6238)
• vacuolar degeneration of motoneurons also in the lower brain stem (cerebellar, reticular, vestibular, cortical, and olfactory involvement variable)
(J:6388)
• number of degenerating neurons increases with development of disease, none before onset of symptoms
(J:19087)
|
|
• loss of large diameter nerve fibers in the median nerve
|
|
• loss of large diameter nerve fibers
|
|
• numbers of myelinated nerve fibers in the nerves to the arm and in the nerve to the tibialis anterior muscle were reduce 67-82%
|
demyelination
(
J:5525
)
|
• in conjunction with dissolution of axoplasm and nerve degeneration
|
|
• impaired slow axonal transport affecting neurofilament proteins more than tubulin and actin
(J:8186)
• fast axonal transport rate reduced 25%
(J:14361)
|
|
• levels of thyrotropin releasing hormone in the cervical spinal cord increase with progression of disease
(J:3719)
• early increases in substance P in the hypothalamus, later increases in spinal cord and midbrain
(J:3719)
• variable levels of Met- and Leu-enkephalin over the course of disease progression
(J:3719)
• greater numbers of thyrotrophin releasing hormone neuronal processes in the ventrolateral horn of the spinal cord but decreasing with age
(J:15226)
• reduced acetylcholinesterase containing cells in the ventral horn of the spinal cord
(J:35070)
• substance P elevated in the ventral horn of the spinal cord early but becoming less as the disease progresses
(J:35070)
|
muscle
|
• enlargement of sarcolemmal nuclei which migrate to the center of the muscle fiber
• muscle fibers eventually decrease in diameter
• deposition of fat between atrophied muscle fibers
|
|
• lose of ability to extend paws at wrist
(J:5102)
• atrophy of facial muscle gives a pointed appearance to the snout and results in the ears being laid back
(J:5102)
• muscle atrophy seen by 6-7 weeks of age
(J:5102)
• neurogenic atrophy seen in muscles of mastication, neck, shoulder girdle, and intercostals
(J:6388)
|
|
• atrophy of facial muscle gives a pointed appearance to the snout and results in the ears being laid back
|
|
• by fourth or fifth week
• particularly involves forelimbs
|
reproductive system
 |
• sperm motility reduced to occasional trembling of the tail
|
|
|
• testis weight 72% of normal
|
|
|
• sperm numbers 70-80% of controls
|
|
|
• lack of intact acrosome
• round sperm heads
|
|
• both sexes sterile
(J:165)
|
homeostasis/metabolism
|
• decreased levels in both sexes
|
|
• cGMP levels decreased 80% in cervical spinal cord, 56% in the cerebellum, and 29% in the cortex
|
craniofacial
|
• atrophy of facial muscle gives a pointed appearance to the snout and results in the ears being laid back
|
upturned snout
(
J:6388
)
|
• upward pointed snout
|
liver/biliary system
|
• vacuolar changes in hepatocytes
|
cellular
|
• all in degenerating neurons
• increase in randomly organized neuronal cytoplasmic microtubules, filaments or smooth endoplasmic reticulum
• membrane bound dense bodies and /or lipid droplets
|
|
|
• sperm numbers 70-80% of controls
|
|
|
• lack of intact acrosome
• round sperm heads
|
|
• reduction and disorganization of rough endoplasmic reticulum
|
|
• increased numbers of lysosomes and autophagic vacuoles
|
|
|
• sperm motility reduced to occasional trembling of the tail
|
endocrine/exocrine glands
|
|
• testis weight 72% of normal
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Werdnig-Hoffmann disease | DOID:13137 |
OMIM:253300 |
J:6388 | |
