Hypersensitive knockin mouse strains identify receptors and pathways for nicotine action.
Two series of knockin mouse strains have been constructed with point mutations that result in hypersensitive neuronal nicotinic acetylcholine receptors containing alpha 4- or alpha 7-subunits. The full expression of the stronger alleles produces neonatal excitotoxic lethality; however, mice with attenuated expression or milder alleles are viable, and display a range of hypersensitive responses to nicotine. To date, measurements have been made on nicotine-induced seizures, Straub tail, hypothermia, antinociception, electroencephalograms and cellular electrophysiological responses. These strains are helping to define the occurrence of these important receptor subtypes, and their role in the acute and chronic actions of nicotine. The hypersensitive strains may be useful for the development of nicotinic drug therapy.
California Institute of Technology, Division of Biology, Pasadena, CA 91125, USA. lester@caltech.edu
Henry A
HA
Lester
Carlos
C
Fonck
Andrew R
AR
Tapper
Sheri
S
McKinney
M Imad
MI
Damaj
Seth
S
Balogh
Jeremy
J
Owens
Jeanne M
JM
Wehner
Allan C
AC
Collins
Cesar
C
Labarca
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics*; D023421:Models, Animal; D009538:Nicotine / Q000009:adverse effects / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000009:adverse effects / Q000494:pharmacology*; D017354:Point Mutation; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000209:etiology / Q000235:genetics; D064569:alpha7 Nicotinic Acetylcholine Receptor
D009538:Nicotine; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579166:Chrna7 protein, mouse