The mouse fidgetin gene defines a new role for AAA family proteins in mammalian development

The mouse mutation fidget arose spontaneously in a heterogeneous albino sto ck(1). This mutant mouse is characterized by a side-to-side head-shaking an d circling behaviour, due to reduced or absent semicircular canals(2). Fidg et mice also have small eyes, associated with cell-cycle delay and insuffic ient growth of the retinal neural epithelium(3,4) and lower penetrance skel etal abnormalities, including pelvic girdle dysgenesis, skull bone fusions and polydactyly(2,5). By positional cloning, we found the gene mutated in f idget mice, fidgetin (Fign), which encodes a new member of the 'meiotic'(6) or subfamily-7 (SF7; ref. 7) group of ATPases associated with diverse cell ular activities (AAA proteins). We also discovered two closely related mamm alian genes. AAA proteins are molecular chaperones that facilitate a variet y of functions, including membrane fusion, proteolysis, peroxisome biogenes is. endosome sorting and meiotic spindle formation(8), but functions for th e SF7 AAA proteins are largely unknown. Fidgetin is the first mutant AAA pr otein found in a mammalian developmental mutant, thus defining a new role f or these proteins in embryonic development.