Mouse Genome Informatics
hm1
    Vegfatm2Pec/Vegfatm2Pec
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 60% die before or around birth while the remaining 40% survive more than 23 months
• 60% die before or around birth while the remaining 40% survive more than 23 months

growth/size
• surviving mutants are about 25% smaller at birth
• surviving mutants gain about 45% less weight than wild-type

behavior/neurological
• mutants develop coarse fur indicative of impaired grooming
• mutants have difficulty turning over when placed on their backs at 5 months of age and can hardly turn over at all by 15 months of age
• when lifted by the tail, mutants reflexively contract their limbs to the trunk and remain immobile
• in the grid test, mutants fall off the grid much quicker than wild-type
• mutants perform worse in the rotating axle test, falling off much quicker than wild-type
• mutants have difficulties in grabbing a horizontal thread with their hindlimbs and hang immobile, while wild-type immediately grab the thread
• mutants are less active at night and for much shorter periods than wild-type
• mutants slap their paws while walking and have a waddling gait
• severely paralysis after ischemic insult by clamping the aortic arch, left subclavian artery and internal mammary artery for only 8 min
• no recovery neurologically
• mutants show progressive signs of limb paresis
• older males are sexually inactive, possibly due to motor dysfunction (J:69797)

muscle
• progressive skeletal muscle fiber atrophy after 4 months of age; atrophy is specific for extrafusal muscle fibers and does not affect muscle spindles or cardiac muscle fibers
• however show no signs of fiber necrosis, sarcomere lysis or sarcolemma disruption, fatty infiltration, fibrosis or dystrophic calcification
• the ankle dorsal flexor muscles of old mice generate only 65% of the maximal force upon tetanic stimulation
• latencies of compound muscle action potentials are slightly increased
• mutants become progressively less mobile and show signs of severe muscle weakness and limb paresis
• muscle weakness is not due to impaired oxygenation or reduced levels of hemoglobin

nervous system
• prominent reactive astrocytosis in the ventral horn of the spinal cord is seen beyond 7 months of age
• focal spheroid axon swellings often occur in several cranial motor nerves and in the ventral horns of the spinal cords beyond 7 months of age
• mutants show features of Wallerian degeneration, including shrunken vacuolated axoplasm, disorganized neurofilaments, few abnormal mitochondria, endoneural fibrosis, and infiltration of macrophages
• aberrant neurofilament accumulation is seen in the motor, but not sensory, nuclei or roots of several cranial nerves in mutants older than 7 months of age
• phrenic nerves progressively lose their large myelinated Agamma motor axons, which innervate the extrafusal muscle fibers
• sciatic nerves progressively lose their large myelinated Agamma motor axons, which innervate the extrafusal muscle fibers
• phosphorylated neurofilament inclusions are seen in the ventral horns of older mutants
• neurodegeneration is due to reduced neural vascular perfusion
• surviving mutants appear healthy until 5 months of age, when they develop progressive motor neuron degeneration of lower motor neurons
• motor neuron degeneration occurs especially in the ventral horn of the spinal cord (30% loss at 17 months) and the motor nuclei in the brain stem
• loss of motor axons in peripheral nerves
• sciatic and phrenic nerves progressively lose their large myelinated Agamma motor axons, which innervate the extrafusal muscle fiber

reproductive system

skeleton

cardiovascular system
• in skeletal muscle, capillary lumen sizes are smaller
• however, capillary-to-muscle ratios, fluoroangiography, and microvascular partial oxygen pressure were normal, indicating that motor neuron degeneration is not secondary to muscle ischemia
• laser Doppler measurements show that baseline neural blood flow is lower than in wild-type, even though the neural vascular flow similarly increases by about 40% in response to hypercapnia, indicating a deficit in neural vascular perfusion

integument
• mutants develop coarse fur indicative of impaired grooming

respiratory system
• a small fraction of mutants that die at birth exhibit lung prematurity
• in a small fraction of mutants, a significantly increased alveolar septal thickness is noted at birth
• in a small fraction of mutants, lung aeration (percentage of total surface filled with air) fails to increase after birth

Mouse Models of Human Disease
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 1; ALS1 105400 J:69797


Mouse Genome Informatics
cx2
    Tg(SOD1*G93A)1Gur/0
Vegfatm2Pec/Vegfatm2Pec

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die earlier (107 3 d) than Tg(SOD1*G93A)1Gur mice

muscle
• worse muscle weakness than Tg(SOD1*G93A)1Gur mice

behavior/neurological
• perform worse in the rotarod test (unable to stay for 2 min on the rotarod beyond 98 2 d) than Tg(SOD1*G93A)1Gur mice