Table 2.

GNB genes have been studied in different model organisms. The table lists phenotypic manifestations resulting from complete (knock-out, KO) or partial (knock-down, KD) lack of each of the five GNB genes. “HET” refers to mouse models carrying only one functional copy of the gene, and “Dup” concerns the presence of three copies. Of note, in Zebrafish each of the genes has two paralogs, as a result of an ancient genome duplication event. In Drosophila melanogaster and C. elegans only two definite homologues have been identified, one corresponding to human GNB1-4 and one corresponding to human GNB5, in each species. NA indicates “Not Available” model.

Gene Name (HGNC)	Annotated Terms in Animal Models
	M. Musculus	Zebrafish	D. Melanogaster	C. elegans
GNB1	(Gnb1): abnormal brain morphology and size (KO) [52]	(gnb1a/gnb1b): altered regulation of neutrophil migrations and posterior lateral line neuromast primordium migration (KD) [54]	(CG10545): abnormal spindle size (KD and overexpression) [55]	(gpb1): essential for embryo development (50–80% embryonic lethality); uncoordinated phenotype in surviving adult worms; functions in establishment of mitotic spindle orientation; expressed in alimentary system, body wall musculature, epithelial system, nervous system and reproductive organs (KD) [56,57]
GNB2	(Gnb2): abnormal behavioral response to light, increased heart rate, shortened PQ interval, shortened RR interval, shortened ST segment (KO) [52]	NA
GNB3	(Gnb3): abnormal eye electrophysiology, mild bradycardia (KO); weight gain (Dup) [58,59,60]	(gnb3a): expressed throughout development; (gnb3b) expressed in the cones of the dorsal and medial retina (KD) [61]
GNB4	(Gnb4): enlarged heart and spleen (KO) [52]	NA
GNB5	(Gnb5): pre-weaning lethality with incomplete penetrance, decreased body size, slow post-natal weigh gain and abnormal vision (KO); increased body weight, adiposity, insulin resistance and liver steatosis (HET) [62,63,64,65]	(gnb5a/gnb5b): abnormal heart contraction, optokinetic behavior and swimming behavior (KO) [66]	(CG10763): pain responsive defective (KD) [67]	(gpb-2): behavioral defects, e.g., delayed egg laying, locomotion, and pharingeal pumping (KO and overexpression) [68]