All Phenotypes Tg(Thy1-FUS*)1Dit MGI Mouse

premature death ( J:287782 )

• shorter life span, with mice starting to die around 20 weeks of age and 50% survival at 50-60 weeks of age

impaired cued conditioning behavior ( J:277077 )

• in the cue-retention condition of the trace fear-conditioning test, 13-week-old mice spend less time freezing than controls when receiving the first and second tone but show normal levels of freezing upon the third tone, indicating that fear memory is retained and retrieved following repetition of the cue and suggesting that impairment of 24-hour memory function is due to impairment in the retrieval of stored memory rather than due to disrupted encoding or consolidation of the information

limb grasping ( J:287782 )

• mice develop an abnormal hindlimb reflex, characterized by hindlimb retraction when lifted by the tail from 12 weeks of age

tremors ( J:287782 )

• mice show unstable walking and tremor-like movements that become increasing severe with age

impaired coordination ( J:287782 )

• mice show progressive motor impairment on the accelerating rotarod which appears at 20 weeks of age

weakness ( J:287782 )

• mice show progressive motor weakening on the hanging wire test at about 20 weeks of age

abnormal gait ( J:287782 )

• mice show abnormal gait, with irregularly spaced shorter strides and uneven left-right step pattern at 1 year of age

short stride length ( J:287782 )

• mice show irregularly spaced shorter strides at 1 year of age

hyperactivity ( J:277077 )

• in the home cage test, 9- to 11-week-old mice do not show differences in total locomotor activity over 3 days, however at the first adaptation period, mice show higher activity levels compared to controls indicating hyperactivity in the novel environment

• in the open field test, 9- to 11-week-old mice show greater movement distances, durations, and speed

• while the number of arm selections in the Y-maze test does not differ in 11-week-old mice, the total number of arm selections is higher and mice travel longer distances and at greater speeds indicating hyperactivity

impaired social recognition ( J:277077 )

• in the three-chamber test, 12-week-old mice spend almost the same amount of time in the chamber with the novel mouse as with that of the familiar mouse during the third phase of the test, indicating that mice fail to distinguish novel and familiar mice and a deficit in social memory

microgliosis ( J:287782 )

• microgliosis in the frontal cortex

microgliosis ( J:287782 )

• microgliosis in the frontal cortex

microgliosis ( J:287782 )

• microgliosis in the frontal cortex

astrocytosis ( J:287782 )

• reactive astrocytosis in the frontal cortex

abnormal neuron morphology ( J:287782 )

• the number of nuclear bodies known as Gemini of coiled bodies in cortical neurons of motor cortex is reduced

motor neuron degeneration ( J:287782 )

• neuronal loss is seen at 1 year of age, but not at 15 weeks of age, even in mice showing early motor deficits

• decrease of spinal motor neurons is not seen until at least 1 year of age, indicating that degeneration of lower motor neurons is not prominent until at least 1 year

abnormal dendritic mushroom spine morphology ( J:277077 )

• the number of mushroom-shaped mature spines is decreased in the frontal cortex and hippocampus

decreased dendritic spine density ( J:277077 )

• mice show decreased total spine density in the frontal cortex and hippocampus at 15 weeks of age

• however, the ratio of mature spines to all spines does not differ, indicating that spine formation, not maturation, is impaired

abnormal postsynaptic density morphology ( J:277077 )

• synaptic density is decreased in the frontal cortex and hippocampus of 15-week-old mice

neuronal cytoplasmic inclusions ( J:277077 , J:287782 )

• accumulation/aggregation of exogenous human protein predominantly in the frontal cortex, hippocampus, and entorhinal cortex and localized to the cytoplasm in 15-week-old mice (J:277077)

• mice show cytoplasmic aggregation/accumulation of the human FUS protein in cortex and pyramidal tract of the spinal cord (J:287782)

abnormal miniature excitatory postsynaptic currents ( J:277077 )

• frequency of miniature excitatory postsynaptic currents (mEPSCs) is reduced in layer V pyramidal neurons from 15-week-old mice

• however, the amplitude of mEPSCs is not different from controls, indicating that the total number of excitatory synaptic inputs is reduced

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

♀	phenotype observed in females
♂	phenotype observed in males
N	normal phenotype

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
amyotrophic lateral sclerosis type 6		DOID:0060198	OMIM:608030	J:277077 , J:287782

Contributing Projects: 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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