Breeding strategies were devised to generate wild type (WT), Angelman Syndrome (Ube3Am-/p+, AS), Ephexin5 knockout (Ephexin5−/−, E5−/−) and double knockout (Ube3Am-/p+/Ephexin5−/−, AS/E5−/−). The gene discussed is ARHGEF15; the disease is Angelman syndrome.