Mouse Genome Informatics
tg1
    Tg(Thy1-Sncg)HvP36Putt/Tg(Thy1-Sncg)HvP36Putt
C57BL/6-Tg(Thy1-Sncg)HvP36Putt
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice do not survive beyond 16 months

behavior/neurological
• at 6 to 9 months
• following paresis
• earlier than 6 months
• earlier than 6 months
• at 6 to 9 months
• at 6 to 9 months
• at 6 months
• following paresis
• at 9 to 16 months, mice develop paresis unlike wild-type mice with earlier development in forelimbs than in hindlimbs

nervous system
• mice exhibit aggregation and fibrillation of gamma-synuclein in the nervous system unlike wild-type mice
• abnormal gamma-synuclein structures are most abundant in the spinal cord
• in the spinal cord gray matter of severely affected and older mice
• at 12 months, motor neuron numbers in severely affected mice are less than 40% of wild-type
• motor neuron loss corresponds to severity of motor impairment

homeostasis/metabolism
• in the spinal cord or brain tissue when mild clinical signs of pathology are apparent
• the number of inclusions increases as clinical phenotypes worsen


Mouse Genome Informatics
tg2
    Tg(Thy1-Sncg)HvP36Putt/0
C57BL/6-Tg(Thy1-Sncg)HvP36Putt
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mice develop motor dysfunction compared with wild-type mice with greater latency and slower progression than homozygous mice
• after 18 months of age, mice exhibit impaired performance on a rotarod compared with wild-type mice
• at 18 months, mice have shorter strides than wild-type mice

nervous system
• in older mice
• motor neuron loss corresponds to severity of motor impairment

homeostasis/metabolism
• in the spinal cord or brain tissue when mild clinical signs of pathology are apparent
• the number of inclusions increases as clinical phenotypes worsen


Mouse Genome Informatics
tg3
    Tg(Thy1-Sncg)HvP36Putt/?
C57BL/6-Tg(Thy1-Sncg)HvP36Putt
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• retinal ganglion cells do not exhibit deterioration or loss despite overexpression of gamma-synuclein (J:185793)
• gliosis is observed within motor regions of cortex
• observed in the trigeminal motor nucleus in affected 12 month old mice
• observed in the trigeminal motor nucleus in affected 12 month old mice
• loss of motor neurons is observed in the trigeminal motor nucleus, but not in the facial and abducens motor nuclei
• neuron loss is observed in select upper and lower motor neuron populations of the motor cortex, and to a lesser degree in the somatosensory regions
• neuron loss is correlated with perikaryal and axonal accumulation of gamma-synuclein, accumulation of detergent-insoluble species and gliosis
• damage to myelin sheath is observed in substantial numbers of myelinated fibers from the sciatic nerve in severely affected mice
• selective neuronal dystrophy is observed in the cortex
• significant neuron loss is observed in affected 12 month old mice
• mice exhibit high levels of astrogliosis and microgliosis in the trigeminal motor nucleus
• some abnormal myelinated fibers and phagocytes are observed in the dorsal spinal root
• however, the majority of myelinated fibers are similar to control in number and condition
• deterioration and loss of myelinated axons in severely affected mice
• reduction in total numbers of myelinated fibers in severely affected mice
• reduced levels of neurofilament proteins, alpha tubulin, and myelin basic protein are observed in severely affected mice
• active Wallerian-like degeneration of the sciatic nerve is observed
• mildly affected mice exhibit slight changes in morphology, but no loss of fibers
• deterioration and loss of myelinated fibers in severely affected mice
• significant decrease in mean myelinated fiber size (49.5%) found in remaining myelinated fibers
• extensive phagocyte infiltration

hematopoietic system
• observed in the trigeminal motor nucleus in affected 12 month old mice

immune system
• observed in the trigeminal motor nucleus in affected 12 month old mice

Mouse Models of Human Disease
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 1; ALS1 105400 J:185793