Objectives: To determine the phenotypic consequences of intermediate levels of Gabrb3 expression.
Methods: ShRNA-mediated Gabrb3-knockdown animals were generated on a C57Bl/6 background. Behavioral phenotypes were assessed in these, heterozygous gene knockout and wild-type control animals using standard protocols, including activity (wheel-running), anxiety (open field), exploratory (place preference & T-maze), socialization (interest, preference & memory: tethered & free interactions) and perseveration (radial maze).
Results: As expected, both Gabrb3-knockdown (KD) and heterozygous knockout (+/-) animals show behavioral differences from wild-type C57Bl/6 animals, with Gabrb3-KD animals exhibiting a phenotypic spectrum intermediate between Gabrb3+/- and total-knockout (KO) animals. Post-natal lethality or gender imbalance in KD animals is not evident, but cannot be ruled out in the founder generation due to small numbers. Unlike Gabrb3+/- animals, Gabrb3-KD animals exhibit hyperactivity reminiscent of surviving KO animals, but they do not exhibit the severe seizures seen in KO animals.
Conclusions: Phenotypic analyses of sh-mediated Gabrb3 knockdown animals complement studies using knockout and haploinsufficiency models, while avoiding early lethality and parent-of-origin dependent complications.