Their involvement in KS was strongly suggested in 2006 when homozygous Prokr2 knockout mice were shown to have hypogonadotropic hypogonadism due to hypothalamic GnRH deficiency and agenesis or hypoplasia of the olfactory bulbs (Matsumoto et al., 2006). The gene discussed is GNRH1; the disease is hypogonadotropic hypogonadism.