In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 96, No. 10 ( 1999-05-11), p. 5746-5751
Abstract:
The α3 subunit of the neuronal nicotinic acetylcholine receptor
is widely expressed in autonomic ganglia and in some parts of the brain. The α3 subunit can form heteromultimeric ion channels with
other α subunits and with β2 and β4 subunits, but its function in vivo is poorly understood. We prepared a null
mutation for the α3 gene by deletion of exon 5 and found that homozygous (−/−) mice lacked detectable mRNA on Northern
blotting. The −/− mice survive to birth but have impaired growth and increased mortality before and after weaning. The
−/− mice have extreme bladder enlargement, dribbling urination, bladder infection, urinary stones, and widely dilated ocular
pupils that do not contract in response to light. Detailed histological studies of −/− mice revealed no significant abnormalities in
brain or peripheral tissues except urinary bladder, where inflammation was prominent. Ganglion cells and axons were present in bladder and
bowel. Bladder strips from −/− mice failed to contract in response to 0.1 mM nicotine, but did contract in response to electrical
field stimulation or carbamoylcholine. The number of acetylcholine-activated single-channel currents was severely reduced in
the neurons of superior cervical ganglia in −/− mice with five physiologically distinguishable nicotinic acetylcholine receptor
subtypes with different conductance and kinetic properties in wild-type mice, all of which were reduced in −/− mice. The findings in
the α3-null mice suggest that this subunit is an essential component of the nicotinic receptors mediating normal function of the autonomic
nervous system. The phenotype in −/− mice may be similar to the rare human genetic disorder of megacystis–microcolon–intestinal
hypoperistalsis syndrome.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.96.10.5746
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1999
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
