Analysis Tools
mortality/aging
|
• homozygotes continue to display a progressive decline in postnatal survival after day 25, with the last suvivor dying at day 125
|
|
• homozygotes are obtained at a reduced Mendelian frequency immediately after birth (14% vs expected 25%); no significant loss is noted in utero
|
|
• homozygotes start dying at day 5 after birth; only 20% survive to day 25
|
cardiovascular system
|
• homozygotes exhibit loss of normal muscarinic regulation of cardiac L-type calcium channels in ventricular myocytes, suggesting that cardiac failure may be the cause of limited life span
• however, homozygotes display normal electrocardiograms as well as normal muscarinic regulation of atrial K+ channels
|
nervous system
|
• homozygotes display occasional seizures, despite absence of obvious histologic abnormalities in the nervous system
|
|
• surprisingly, homozygotes exhibit a grossly intact nervous system despite the fact that the encoded protein constitutes 0.2-0.5% of brain particulate protein and 10% of the nerve growth cone membrane
• however, mutant ventricular myocytes exhibit loss of muscarinic inhibition of the isoproterenol-stimulated L-type ventricular calcium channel; the L-type calcium channel responds normally to isoproterenol, but muscarinic inhibition is abolished
|
behavior/neurological
|
• homozygotes display occasional seizures, despite absence of obvious histologic abnormalities in the nervous system
|
