Mice that are homozygous for all three targeted mutations die within 24 hours of birth. Although newborn mice are initially capable of directed movements and react to tactile stimuli, the integrative brain functions required for breathing are impaired. At birth, the body and brain weights of triple targeted mutation mice are indistinguishable. Assymetric type I and symmetric type II synapses in triple homozygotes are ultrastructurally normal. The density of symmetric (presumptive inhibitory) synapses are reduced whereas the density of asymmetric (presumptive excitatory) synapses are not. Neurotransmitter release is generally impaired due to reduced Ca<sup>2+</sup> channel function. No protein product from any of the targeted genes is detected in brain tissue. Quantification of the levels of 22 other neuronal proteins detected no major changes. This mutant mouse strain represents a model that may be useful in studies of synaptic vesicle exocytosis mechanisms in neurons. 

Mice that are homozygous for neurexin I, II and III gene mutations die within 24 hours of birth. Although newborn mice are initially capable of directed movements and react to tactile stimuli, the integrative brain functions required for breathing are impaired.

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B6;129-Nrxn3<tm1Sud> Nrxn1<tm1Sud> Nrxn2<tm1Sud>/J Frozen Em