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

A Correction to this article was published on 01 November 2000


The mouse mutation fidget arose spontaneously in a heterogeneous albino stock1. This mutant mouse is characterized by a side-to-side head-shaking and circling behaviour, due to reduced or absent semicircular canals2. Fidget mice also have small eyes, associated with cell-cycle delay and insufficient growth of the retinal neural epithelium3,4, and lower penetrance skeletal abnormalities, including pelvic girdle dysgenesis, skull bone fusions and polydactyly2,5. By positional cloning, we found the gene mutated in fidget mice, fidgetin (Fign), which encodes a new member of the ‘meiotic’6 or subfamily-7 (SF7; ref. 7) group of ATPases associated with diverse cellular activities (AAA proteins). We also discovered two closely related mammalian genes. AAA proteins are molecular chaperones that facilitate a variety of functions, including membrane fusion, proteolysis, peroxisome biogenesis, endosome sorting and meiotic spindle formation8, but functions for the SF7 AAA proteins are largely unknown. Fidgetin is the first mutant AAA protein found in a mammalian developmental mutant, thus defining a new role for these proteins in embryonic development.

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Figure 1: Genetic and physical maps of the Fign locus.
Figure 2: ETn insertion disrupts expression of the fidgetin candidate gene, Fi2.
Figure 3: Construction of a gene-targeted allele of fidgetin.
Figure 4: Expression of fidgetin in heterozygous and homozygous Figntm1Frk mice.
Figure 5: Phylogenetic analysis of the fidgetin subgroup of AAA proteins.

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We thank A. Lupas for help with protein sequence analysis; K. Frohlich for the AAA family web site; J. Gervais and P. Jewett for technical assistance; T. O'Brien, T. Gridley and R. Smith for advice on embryo analysis; T. Gridley and J. Schimenti for comments; and A. Gossler and J. Nadeau for discussions. This work was supported by grants from the NIH (DC03611 to W.N.F., NS32801 to V.A.L.).

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Correspondence to Wayne N. Frankel.

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Cox, G., Mahaffey, C., Nystuen, A. et al. The mouse fidgetin gene defines a new role for AAA family proteins in mammalian development. Nat Genet 26, 198–202 (2000).

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