Although LC3, a mouse homologue of yeast Atg8, has mainly been used for a marker protein of autophagy, little is known about roles of subtypes of LC3, LC3A and LC3B, or whether these proteins compensate their roles for each other during autophagic processes. For this, we produced LC3A and LC3B (LC3A/B)-double deficient (KO) mice, which were born normally and were grown-up to be capable of reproduction. Using these KO mice, both mRNA and protein levels of LC3 homologous proteins, a GABARAP family of proteins, were examined in brain and other tissues and found that they did not significantly alter between wild-type and LC3A/B-double deficient mice, although the expression level of GABARAP only was significantly higher in liver tissue than in brain tissue. These results indicate that basic autophagy may work normally in neurons of LC3A/B-deficient brains. Since we have previously shown that Atg7-deficiency rescues mouse neonatal hippocampal pyramidal neurons from hypoxic-ischemic injury (H/I), LC3A/B-double deficient mice were applied to this H/I model. As previously reported, hippocampal pyramidal neurons in wild-type mice were vulnerable to H/I injury, while the protein amount of LC3-II was markedly elevated from 9 to 24 hours after H/I injury. In contrast, hippocampal pyramidal neurons deficient in LC3A/B were resistant to the H/I injury. These results suggest that LC3A/B, but not GABARAP family of proteins, are involved in H/I injury-mediated pyramidal neuron death that occurs in the hippocampal pyramidal layers of neonatal mouse brains. As shown in our previous study, excess autophagic stress may induce neuron death. Our present data using LC3A/B-deficient mice strongly support the presence of H/I injury-mediated autophagic neuron death in neonatal brains. Of course, further study is required to elucidate the molecular mechanism of why H/I injury-mediated neuron death is suppressed by deficiency in Atg7 or LC3A/B.