Table 1 This table illustrates the similarities and differences in behavior observed in constitutive versus conditional knockout models of Gabrb3 illustrating cell-type specific roles in behavioral diversity.
Animal models | Constitutive Gabrb3 Knockout | Conditional Gabrb3 Knockout; Neuron-specific | Conditional Gabrb3 Knockout; Forebrain-specific | Conditional Gabrb3 Knockout; endothelial cell-specific | Constitutive Gabrb2 Knockout |
|---|---|---|---|---|---|
Gene targeting | Targeted disruption of the β3 locus; Exons 1–3 | Use of Synapsin 1-cre Target: Exon 3 | Use of CamKII-cre Target: Exon 3 | Use of Tie2-cre Target: Exon 3 | Targeted disruption of the β2 locus; Exons 6–7 |
References | Homanics et al., 1997; De Lorey et al.; 1998 | Ferguson et al., 2007 | Ferguson et al., 2007 | Li et al. 2018; Subburaju et al., 2020 | Yeung et al., 2018 |
Time of gene inactivation | Embryonic Day 0 | Embryonic Day 12.5+ | ~ 2 weeks postnatal | Embryonic Day 9+ | Embryonic Day 0 |
Tissue specificity | All cells | Most neurons | Primarily forebrain neurons | Endothelial cells | All cells |
Altered behaviors | Impaired cognitive functions Increased locomotor activity Hyperactive-intense circling pattern Stereotypical behavior | Cognitive functions not tested Locomotor activity not tested No hyperactivity Not reported | Normal cognitive functions Increased locomotor activity Hyper-responsive to human contact Not reported | Impaired cognitive functions-mild Increased locomotor activity Hyperactive-continuous running Stereotypical Behavior | Impaired cognitive functions Increased locomotor activity Hyperactive movement Stereotypical Behavior |
Other behaviors reported | Reduced Etomidate LORR Impaired maternal behavior; foot clasping behavior EEG abnormalities, disturbed rest-activity cycle | Reduced Etomidate LORR Normal maternal behavior; no foot clasping behavior No seizure like activity observed | Reduced Etomidate LORR Impaired maternal behavior; no foot clasping behavior EEG: not tested | Increased anxiety and depression Impaired social communication and social novelty Impaired prepulse inhibition of startle | Reduced affective symptoms Impaired social affiliation and social novelty Impaired prepulse inhibition of startle |
Body size | Runted until weaning | Normal | Some become obese | Runted until weaning | Normal |
Neonatal lethality | 90% die as neonates | 61% die as neonates | 30% die at P15-P25 | No pup mortality | No pup mortality |
Seizure-like activity | Seizures (epilepsy) Multiple seizure types | No tremors or seizures | Occasional absence-like and convulsive seizures | Seizure-like symptoms in 15% mice | Accelerated PTZ-induced seizure; susceptible to audiogenic epilepsy |
Disease similarity | Angelman syndrome or autism spectrum disorder (ASD) | Unclear | ASD | Anxiety, Depression, Schizophrenia, | Schizophrenia |
