Analysis Tools
mortality/aging
|
• about 80% die before 60 days of age on a regular diet
• however, when fed a soft food diet from the second week of life, most pups catch up to the weight of wild-type and survive; these mutants have a normal weight and lifespan
|
growth/size/body
|
• mutants do not gain body weight at the same rate as wild-type, even if fed soft-food diet, but eventually reach a normal body weight
|
behavior/neurological
|
• the latency until onset of myoclonic jerks after application of pentylenetetrazole (PTZ) is almost doubled compared with wild-type and epileptic activity does not progress to generalized seizures
• at higher doses of PTZ or pilocarpine treatment, all mutants recover from epileptic activity unlike wild-type where half die
• onset of hyperthermia-induced generalized epileptic activity in 10 day old pups is delayed compared to wild-type
|
|
• the habituation of exploratory locomotion within new surroundings is delayed
|
|
• in the light-dark test, mutants spend slightly more time in the bright area compared with wild-type
|
|
• exploratory activity in response to a new object (falcon tube) is delayed
|
homeostasis/metabolism
|
• Na+ dependent acid extrusion is severely diminished in choroid plexus epithelial cells; clusters of isolated choroid plexus epithelial cells acid-loaded by an ammonium pulse, then washed-out using saline devoid of Na+, show a diminished Na+-dependent recovery of pHi in the presence of bicarbonate when Na+ was reapplied at the time of peak acidification compared to wild-type
• neuronal pHi regulation is compromised; the rate of pHi recovery in hippocampal CA3 pyramidal cells during the propionate exposure is significantly slower than in wild-type and the alkaline overshoot upon propionate washout is less pronounced
|
nervous system
|
• the latency until onset of myoclonic jerks after application of pentylenetetrazole (PTZ) is almost doubled compared with wild-type and epileptic activity does not progress to generalized seizures
• at higher doses of PTZ or pilocarpine treatment, all mutants recover from epileptic activity unlike wild-type where half die
• onset of hyperthermia-induced generalized epileptic activity in 10 day old pups is delayed compared to wild-type
|
|
• reduction in brain ventricle volume
|
|
• the choroid plexus epithelium shows enlarged lateral intercellular spaces and a reduction of apical microvilli
|
|
• in the CA3 area, propionate-induced intracellular acidification and attenuation of 4-aminopyridine-induced network activity are prolonged in mutants, indicating defects in neuronal excitability
|
