Recent insight into the functional roles of nSMase2 has come from the studies of nSMase2-deficient mice. In 2005, an nSMase2 KO mouse was generated by Stoffel and colleagues. Interestingly, although multiple nSMases exist, disruption of nSMase2 resulted in the loss of the majority of N-SMase activity in many organs of the nSMase2 KO mouse. This confirms that nSMase2 is an important N-SMase physiologically. This was further emphasized by the complete loss of in vitro N-SMase activity in various tissues of a double nSMase1 nSMase2 KO mouse. The nSMase2 KO mouse was characterized by an embryonic and juvenile dwarfism phenotype (Stoffel et al., 2005). This phenotype was most strikingly manifested in the skeleton with knockout animals displaying short statured long bones and joint deformations compared to wild-type animals. Further analysis revealed that nSMase2 knockout animals had lower levels of growth hormone and decreased concentrations of serum insulin-like growth factor and this was speculated to cause the prolonged cell cycle and hypoplasia seen in the KO mice (Stoffel et al., 2005). Further study showed that the defects seen in the nSMase2 KO
