TY - JOUR
T1 - Acetylcholine receptor ε-subunit deletion causes muscle weakness and atrophy in juvenile and adult mice
AU - Witzemann, V.
AU - Schwarz, H.
AU - Koenen, M.
AU - Berberich, C.
AU - Villarroel, A.
AU - Wernig, A.
AU - Brenner, H. R.
AU - Sakmann, B.
PY - 1996/11/12
Y1 - 1996/11/12
N2 - In mammalian muscle a postnatal switch in functional properties of neuromuscular transmission occurs when miniature end plate currents become shorter and the conductance and Ca2+ permeability of end plate channels increases. These changes are due to replacement during early neonatal development of the γ-subunit of the fetal acetylcholine receptor (AChR) by the ε-subunit. The long-term functional consequences of this switch for neuromuscular transmission and motor behavior of the animal remained elusive. We report that deletion of the ε-subunit gene caused in homozygous mutant mice the persistence of γ-subunit gene expression in juvenile and adult animals. Neuromuscular transmission in these animals is based on fetal type AChRs present in the end plate at reduced density. Impaired neuromuscular transmission, progressive muscle weakness, and atrophy caused premature death 2 to 3 months after birth. The results demonstrate that postnatal incorporation into the end plate of ε-subunit containing AChRs is essential for normal development of skeletal muscle.
AB - In mammalian muscle a postnatal switch in functional properties of neuromuscular transmission occurs when miniature end plate currents become shorter and the conductance and Ca2+ permeability of end plate channels increases. These changes are due to replacement during early neonatal development of the γ-subunit of the fetal acetylcholine receptor (AChR) by the ε-subunit. The long-term functional consequences of this switch for neuromuscular transmission and motor behavior of the animal remained elusive. We report that deletion of the ε-subunit gene caused in homozygous mutant mice the persistence of γ-subunit gene expression in juvenile and adult animals. Neuromuscular transmission in these animals is based on fetal type AChRs present in the end plate at reduced density. Impaired neuromuscular transmission, progressive muscle weakness, and atrophy caused premature death 2 to 3 months after birth. The results demonstrate that postnatal incorporation into the end plate of ε-subunit containing AChRs is essential for normal development of skeletal muscle.
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U2 - 10.1073/pnas.93.23.13286
DO - 10.1073/pnas.93.23.13286
M3 - Article
C2 - 8917583
AN - SCOPUS:0029661887
SN - 0027-8424
VL - 93
SP - 13286
EP - 13291
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 23
ER -