Haploinsufficiency is poorly studied in both man and mouse. Furthermore, the study of the occurrence of spina bifida in genes acting in an additive or subtractive manner is almost unknown. Currently, there are 5 studies in the mouse, which have demonstrated spina bifida and the interaction of the involved genes mechanistically. These include Lrp6 and Wnt5a , Zac1 and Suz12 , Hira and Pax3 , Rybp encompassing Ring1 and YYP1 , and haploinsufficiency of the components in the primary cilium of the hedgehog pathway .