Analysis Tools
mortality/aging
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• mice are born in expected Mendelian ratios, appear healthy, and exhibit normal lifespans relative to wild-type controls
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behavior/neurological
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• male mice show normal motor coordination and learning in the accelerating rotarod test, suggesting normal cerebellar function
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• male mice display abnormal sedation responses to alpha2-adrenergic receptor (a spinophilin target) or adenosine A1 receptor (a neurabin-1 target) agonist stimulation in the rotarod assay
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• males show significantly enhanced susceptibility to kainate- and pentylenetetrazole (PTZ)-induced seizures
• after an i.p. injection of kainate, 7 of 8 mice display severe generalized tonic-clonic seizures (phase 4), whereas none of the kainate-injected wild-type controls (0 of 8) reach phase 4
• after a subconvulsive injected dose of PTZ, all (8 of 8) mice exhibit whole-body clonus with a sudden loss of upright posture, whereas none of the PTZ-injected wild-type controls (0 of 8) show generalized clonus (phase 3)
• administration of guanfacine (a partial alpha2A-adrenergic receptor agonist) prior to PTZ injection results in partial improvement of PTZ-induced phenotypes and 3 of 8 mice do not exhibit phase 3 seizures
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• males show enhanced sensitivity to sedation elicited by R-PIA (an adenosine A1 receptor agonist) in the rotarod assay
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• males show significantly decreased sensitivity to sedation elicited by UK-14304 (an alpha2-adrenergic receptor agonist) in the rotarod assay
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• in a classic eyeblink conditioning test, males show normal learning in the delay paradigm but impaired learning in the more complex trace paradigm
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• in the hidden-platform version of the Morris water-maze test and subsequent probe test, males show severely impaired spatial learning even after 10 days of training
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• in the light-dark transition test, male mice show similar or slightly smaller transition numbers and significantly less time spent in the light chamber, indicating enhanced anxiety
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• in the open field test, male mice show significantly less time spent in the center area and more time spent close to the walls, indicating an increased anxiety response
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• miales show an enhanced acoustic startle eyeblink response: % of startle responses during the initial 30-ms period of the conditioned stimulus in eye blink conditioning is significantly higher than in wild-type controls
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• males exhibit striking hyperactivity in the open field test
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• males exhibit significantly increased rearing activity in the open field test
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• in the three-chamber social interaction test, males show significantly less interest in stranger mice, suggesting autistic-like behavior
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nervous system
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• adult male mice show normal brain anatomy with no detectable changes in major synaptic proteins relative to wild-type controls
• 2- to 4-month-old males show normal synaptic density and spine size distribution in the CA1 stratum radiatum, with no changes in spinal head area or PSD length, suggesting normal spine growth and maturation in hippocampal neurons
• basal synaptic transmission, paired-pulse facilitation, and NMDA-R-dependent LTP induced by high-frequency stimulation are unchanged, suggesting normal NMDA-R-dependent synaptic plasticity in the hippocampus
• no significant upregulation of SIPA1L1 paralogs (SIPA1L2 or SIPA1L3) is observed in hippocampal lysates
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• males show significantly enhanced susceptibility to kainate- and pentylenetetrazole (PTZ)-induced seizures
• after an i.p. injection of kainate, 7 of 8 mice display severe generalized tonic-clonic seizures (phase 4), whereas none of the kainate-injected wild-type controls (0 of 8) reach phase 4
• after a subconvulsive injected dose of PTZ, all (8 of 8) mice exhibit whole-body clonus with a sudden loss of upright posture, whereas none of the PTZ-injected wild-type controls (0 of 8) show generalized clonus (phase 3)
• administration of guanfacine (a partial alpha2A-adrenergic receptor agonist) prior to PTZ injection results in partial improvement of PTZ-induced phenotypes and 3 of 8 mice do not exhibit phase 3 seizures
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