Since experimental evidences of Rodrigues group have shown the importance to investigate this mouse model at the early stages of life, we conducted behavioral, immunohistochemical and molecular studies in animals between 8 and 12 weeks of age. In the present study, we demonstrate for the first time that the a-Gal KO male mice present molecular and structural alterations in pain sensation such as heat/cold-hyperalgesia and mechano-hyperalgesia. In the present work, our main goal was to determine to what extent the alterations of phenotypic traits in mice mutant for this enzyme recapitulate the alterations found in the human disease. To this end, we have used the a-GalA KO mice to characterize different phenotypic, morphological and molecular parameters altered in FD. Due to the X-chromosomal inheritance of FD, heterozygous female carriers can be asymptomatic or clinically affected, usually with a late onset and mild form of the disease. In this context, the most Bekanamycin affected males have little, if any, a-GalA activity and replicate completely the Sulfamerazine clinical manifestation of the disease including angiokeratoma, hypohydrosism, renal failure and pain crises. Nevertheless, it is important to highlight that recently published articles, reflect the shift in this classical view of the expression of FD in females, showing a high number of heterozygous females manifesting clinical signs ranging from mild to very severe frameworks, similar to those found in affected males. From this point of view, in women the age of onset and evolution are generally delayed. This extreme variability depends on the different configurations of X-chromosome inactivation which is tissue-specific and the organ damage in women depends on the degree of mosaicism between healthy and altered cells. Interestingly, Rodrigues et al. found that FD show significantly increased body weight after 24 and 48 weeks in comparison to control WT mice. The same authors claimed about neuronal alterations in FD mice that are difficult to detect at reported ages. Moreover, when 8 week-old a-GalA males were treated by a potent inhibitor of glucosylceramide synthase for 4 weeks, significant changes in the body weight loss were observed.