PMID- 10531434
OWN - NLM
STAT- MEDLINE
DCOM- 19991119
LR  - 20191023
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 19
IP  - 21
DP  - 1999 Nov 1
TI  - Multiorgan autonomic dysfunction in mice lacking the beta2 and the beta4 subunits
      of neuronal nicotinic acetylcholine receptors.
PG  - 9298-305
AB  - Transcripts for the beta2 and the beta4 nicotinic acetylcholine receptor (nAChR) 
      subunits are found throughout the CNS and the peripheral nervous system. These
      two beta subunits can form heteromultimeric channels with any of the alpha2,
      alpha3, alpha4, or alpha5 subunits in heterologous expression systems.
      Nonetheless, the subunit composition of native nAChRs and the role of different
      nAChR subtypes in vivo remain unclear. We prepared null mutations for the beta2
      and the beta4 genes and bred beta2-/-beta4-/- mice by mating mice of identical
      beta2-/-beta4+/- or beta2+/-beta4-/- genotype. The beta2-/- and the beta4-/-
      single-mutant mice grow to adulthood with no visible phenotypic abnormalities.
      The beta2-/-beta4-/- double mutants survive to birth but have impaired growth and
      increased perinatal mortality. They also present enlarged bladders with dribbling
      urination and develop urinary infection and bladder stones. The ocular pupils are
      widely dilated and do not constrict in response to light. Histological studies
      revealed no significant abnormalities of brain or peripheral tissues except for
      hyperplasia in the bladder mucosa of beta4-/- and beta2-/-beta4-/- mutants.
      Bladder strips from beta2-/-beta4-/- mice did not respond to nicotine but
      contracted when stimulated with a muscarinic agonist or electric field
      stimulation. Bladder strips from beta4 mutants did not respond to nicotine
      despite the absence of major bladder dysfunction in vivo. Acetylcholine-activated
      whole-cell currents were absent in superior cervical ganglion neurons from
      beta2-/-beta4-/- mice and reduced in neurons from beta4-/- mice. Although there
      is apparent redundancy and a superficially normal phenotype in beta2-/- and
      beta4-/- mice, physiological studies indicate major deficits in the beta4-/-
      mice. Our previous description of a similar phenotype in alpha3-/- mice and the
      current data suggest that the alpha3 and the beta4 subunits are major components 
      in autonomic nAChRs. The phenotype of the beta2-/-beta4-/- and alpha3-/- mice
      resembles the autosomal recessive megacystis-microcolon-hypoperistalsis syndrome 
      in humans.
FAU - Xu, W
AU  - Xu W
AD  - Department of Molecular Genetics, Baylor College of Medicine, Houston, Texas,
      77030, USA.
FAU - Orr-Urtreger, A
AU  - Orr-Urtreger A
FAU - Nigro, F
AU  - Nigro F
FAU - Gelber, S
AU  - Gelber S
FAU - Sutcliffe, C B
AU  - Sutcliffe CB
FAU - Armstrong, D
AU  - Armstrong D
FAU - Patrick, J W
AU  - Patrick JW
FAU - Role, L W
AU  - Role LW
FAU - Beaudet, A L
AU  - Beaudet AL
FAU - De Biasi, M
AU  - De Biasi M
LA  - eng
GR  - HD-24064/HD/NICHD NIH HHS/United States
GR  - NS-13546/NS/NINDS NIH HHS/United States
GR  - NS-22061/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for
      Neuroscience
JID - 8102140
RN  - 0 (Macromolecular Substances)
RN  - 0 (Receptors, Nicotinic)
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Animals
MH  - Autonomic Nervous System Diseases/*genetics/physiopathology
MH  - Cells, Cultured
MH  - Crosses, Genetic
MH  - Exons
MH  - Eye Abnormalities/genetics/pathology
MH  - Female
MH  - Genomic Library
MH  - Introns
MH  - Macromolecular Substances
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Mucous Membrane/abnormalities/pathology
MH  - Neurons/drug effects/*physiology
MH  - Nicotine/pharmacology
MH  - Receptors, Nicotinic/deficiency/genetics/*physiology
MH  - Superior Cervical Ganglion/physiology/*physiopathology
MH  - Urinary Bladder/abnormalities/pathology
PMC - PMC6782888
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
PST - ppublish
SO  - J Neurosci. 1999 Nov 1;19(21):9298-305.