Phenotypes for Htr2c MGI:2175216 MGI Mouse

premature death ( J:24339 )

• male hemizygotes are prone to sudden death from seizures

• spontaneous deaths are first observed in the fifth week after birth

• survival rate continues to decline thereafter, such that less than 60% survival is noted at 25 weeks of age

• however, deaths are not preceded by any obvious health problems

• male hemizygotes show a 13% increase in average total body mass relative to wild-type controls, with no difference in body length

• in rare cases, male hemizygotes weigh twice as much as wild-type siblings, attaining a weight of up to 82 g

• when fed ad libitum, male hemizygotes weigh significantly more than wild-type controls, with no significant changes in body length

• however, when pair-fed for 4 weeks postweaning and fasted overnight, male hemizygotes that have been provided only the amount of food consumed by their wild-type partners show no differences in body mass, length, white adipose tissue deposits, or plasma glucose and insulin levels relative to wild-type littermates that have been fed ad libitum

increased white adipose tissue amount ( J:24339 )

• male hemizygotes display significantly larger white adipose tissue deposits than wild-type controls

• in contrast, brown adipose tissue weights are not significantly altered

increased epididymal fat pad weight ( J:24339 )

• male hemizygotes show a >30% increase in epididymal white adipose tissue deposits relative to wild-type controls

increased renal fat pad weight ( J:24339 )

• male hemizygotes show a 48% increase in perirenal white adipose tissue deposits relative to wild-type controls

behavior/neurological phenotype ( J:24339 )

N	• hemizygous males display normal sensitivity to thermal and mechanical nociceptive stimuli relative to wild-type controls

increased susceptibility to pharmacologically induced seizures ( J:24339 )

• in response to i.v. infusion of metrazol (an epileptogenic GABA_A receptor antagonist) at a constant rate, 11-15 week old male hemizygotes display a 24% reduction in seizure threshold (onset of first twitch response), an 83% decrease in the duration of the tonic-clonic phase, and a 48% decrease in the lethal dose, relative to wild-type controls

impaired behavioral response to xenobiotic ( J:24339 )

• o unlike wild-type controls where i.p. admninistration of the serotonergic agonist m-chlorophenylpiperazine (mCPP, 5 mg/kg) reduces food intake by 78%, male hemizygotes are resistant to the appetite suppresant (anorectic) actions of mCPP

polyphagia ( J:24339 )

• male hemizygotes display increased food consumption as a result of a behavioral disorder rather than a metabolic defect

increased grooming behavior ( J:24339 )

• spontaneous seizures are often preceded by repetitive grooming of the snout

tonic seizures ( J:24339 )

• occasionally, seizures progress to a tonic extension phase, resulting in respiratory arrest and death within seconds of seizure onset

tonic-clonic seizures ( J:24339 )

• after the initial repetitive grooming activity, male hemizygotes fall on their sides and progress to hyperkinetic tonic-clonic seizures

• in most cases, hemizygotes recover quickly and resume a normal behavior; this cycle may be repeated over the next few minutes

sporadic seizures ( J:24339 )

• male hemizygotes display spontaneous epileptic seizures, with a frequency not greater than 2 or 3 per day

nervous system phenotype ( J:24339 )

N	• hemizygous males display normal brain cytoarchitecture and ventricular size relative to wild-type controls • no differences in hippocampal LTP are observed in the CA1 and CA2 regions relative to wild-type controls