TY - JOUR
T1 - Targeted disruption of NMDA receptor 1 gene abolishes NMDA response and results in neonatal death
AU - Forrest, Douglas
AU - Yuzaki, Michisuke
AU - Soares, Holly D.
AU - Ng, Lily
AU - Luk, Daniel C.
AU - Sheng, Morgan
AU - Stewart, Colin L.
AU - Morgan, James I.
AU - Connor, John A.
AU - Curran, Tom
PY - 1994/8
Y1 - 1994/8
N2 - In vitro studies have suggested that the NMDA receptor consists of an essential subunit, NR1, and various modulatory NR2 subunits. To test this hypothesis directly in vivo, we generated mice carrying a disrupted NR I allele. NMDA-inducible increases in intracellular calcium and membrane currents were abolished in neurons from homozygous null mutants (NR1-/-). Thus, NR1 has a unique role, which cannot be substituted by any other subunit, in determining the activity of the endogenous NMDA receptor. A concomitant reduction in levels of NR2B but not NR2A occurred in NR1-/- mice, demonstrating that there is an interdependence of subunit expression. NR1-/- mice died 8-15 hr after birth, indicating a vital neonatal function for the NMDA receptor. Although the NMDA receptor has been implicated in several aspects of neurodevelopment, overall neuroanatomy of NR1-/- mice appeared normal. Pathological evidence suggested that respiratory failure was the ultimate cause of death.
AB - In vitro studies have suggested that the NMDA receptor consists of an essential subunit, NR1, and various modulatory NR2 subunits. To test this hypothesis directly in vivo, we generated mice carrying a disrupted NR I allele. NMDA-inducible increases in intracellular calcium and membrane currents were abolished in neurons from homozygous null mutants (NR1-/-). Thus, NR1 has a unique role, which cannot be substituted by any other subunit, in determining the activity of the endogenous NMDA receptor. A concomitant reduction in levels of NR2B but not NR2A occurred in NR1-/- mice, demonstrating that there is an interdependence of subunit expression. NR1-/- mice died 8-15 hr after birth, indicating a vital neonatal function for the NMDA receptor. Although the NMDA receptor has been implicated in several aspects of neurodevelopment, overall neuroanatomy of NR1-/- mice appeared normal. Pathological evidence suggested that respiratory failure was the ultimate cause of death.
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U2 - 10.1016/0896-6273(94)90350-6
DO - 10.1016/0896-6273(94)90350-6
M3 - Article
C2 - 8060614
AN - SCOPUS:0028030468
VL - 13
SP - 325
EP - 338
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 2
ER -