These Uba6flox/flox mutant mice possess loxP sites flanking exons 16-17 of the ubiquitin-like modifier activating enzyme 6 (Uba6) gene. Uba6 (E1) is part of the ubiquitin proteasome system (UPS) which regulates protein homeostasis during development. Complete UBA6 deficiency leads to embryonic arrest by E5.5. Mice that are homozygous for this floxed-allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 3-6 deleted in the cre-expressing tissues. For example, when bred to B6.Cg-Tg(Nes-cre)1Kln/J mice (Stock No.003771), resulting mice lack neuronal UBA6 and display altered neuronal patterning in the hippocampus and the amygdala, decreased dendritic spine density, and numerous behavioral disorders. They also contain altered levels of ubiquitin protein ligase E3A (Ube3a) and SH3/ankyrin domain gene 3 (Shank3) spine proteins.