Mouse Genome Informatics
tg
    Tg(CAG-dsRed2/RNAi:Tardbp)6Zxu/0
involves: C57BL/6 * C57BL/6J * FVB/NJ * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• 17.4% of males, and no females, have a short lifespan and die with hindlimb paralysis at a mean of 38.9 days
• 25% of males and 15.6% of females show sudden death without paralysis with a mean of 33.6 days and 41.3 days in females and males, respectively
• 57.6% of males and 84.4% of females survive longer (mean of 80-83 days) and die with whole body paralysis

behavior/neurological
• discoordinated movements
• mice show reduced vertical behaviors by 5 weeks of age
• mice exhibit hyperactivity beginning at 4 weeks of age, which peaks at around 5 weeks of age and ends around 10 weeks of age
• after 10 weeks of age, mice are less active as they become progressively weaker
• unsteady gait
• mice surviving the longest develop whole-body paralysis; this is seen in both males and females
• 17.4% of males, and no females, have a short lifespan and die with hindlimb paralysis

cardiovascular system

growth/size
• mice start to lose weight around 5 weeks of age

hematopoietic system
• abundant microgliosis in the ventral horn gray matter

immune system
• abundant microgliosis in the ventral horn gray matter

muscle
• necrotic skeletal muscle fibers and fibers with centralized nuclei in some areas of the muscle
• necrotic skeletal muscle fibers and fibers with centralized nuclei in some areas of the muscle
• electromyography indicates that mice develop progressive active denervation of muscles as indicated by the presence of positive sharp waves

nervous system
• abundant microgliosis in the ventral horn gray matter
• astrogliosis in the deep layer of the frontal cortex
• abundant astrogliosis in the ventral horn gray matter
• neurodegeneration in layer V cortex and ventral horn spinal cord
• dramatic motor neuron loss, with about 60% fewer motor neurons in the ventral horn
• degeneration of axons in the ventral but not dorsal roots

Mouse Models of Human Disease
OMIM IDRef(s)
Amyotrophic Lateral Sclerosis 10, with or without Frontotemporal Dementia; 612069 J:207750