The mouse fidgetin gene defines a new role for AAA family proteins in mammalian development (original) (raw)

Nature Genetics volume 26, pages 198–202 (2000)Cite this article

A Correction to this article was published on 01 November 2000

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Gruneberg, H. Two new mutant genes in the house mouse. J. Genet. 45, 22–28 (1943).
    Article Google Scholar
  2. Truslove, G.M. The anatomy and development of the fidget mouse. J. Genet. 54, 64–86 (1956).
    Article Google Scholar
  3. Konyukhov, B.V. & Sazhina, M.V. The cell cycle and retinal histogenesis in fidget mutant mice. Dev. Biol. 54, 13–22 (1976).
    Article CAS Google Scholar
  4. Konyukhov, B.V. & Sazhina, M.V. Effect of the fidget gene on cell proliferation in the brains of mouse embyros. Genetika 8, 79–83 (1972).
    Google Scholar
  5. Gruneberg, H. Genetical studies on the skeleton of the mouse. XV. Relations between major and minor variants. J. Genet. 53, 515–533 (1955).
    Article Google Scholar
  6. Swaffield, J.C. & Purugganan, M.D. The evolution of the conserved ATPase domain (CAD): reconstructing the history of an ancient molecule. J. Mol. Evol. 45, 549–563 (1997).
    Article CAS Google Scholar
  7. Beyer, A. Sequence analysis of the AAA protein family. Prot. Sci. 6, 2043–2058 (1997).
    Article CAS Google Scholar
  8. Patel, S. & Latterich, M. The AAA team: related ATPases with diverse functions. Trends Cell Biol. 8, 65–71 (1998).
    Article CAS Google Scholar
  9. Clark-Maquire, S. & Mains, P.E. Mei-1 a gene required for meiotic spindle formation in Caenorhabditis elegans, is a member of a family of ATPases. Genetics 136, 53–546 (1994).
    Google Scholar
  10. Letts, V.A. et al. The mouse stargazer gene encodes a neuronal Ca2+ channel γ subunit. Nature Genet. 19, 340–347 (1998).
    Article CAS Google Scholar
  11. Muller, J.M.M. et al. The mouse p97 (CDC48) gene. Genomic structure, definition of transcriptional regulatory sequences, gene expression, and characterization of a pseudogene. J. Biol. Chem. 274, 10154–10162 (1999).
    Article CAS Google Scholar
  12. Hazan, J. et al. Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nature Genet. 23, 296–303 (1999).
    Article CAS Google Scholar
  13. Hartman, J.J. et al. Katanin, a microtubule-severing protein, is a novel AAA ATPase that targets to the centrosome using a WD40-containing subunit. Cell 93, 277–87 (1998).
    Article CAS Google Scholar
  14. Yu, R.C., Hanson, P.I., Jahn, R. & Brünger, A.T. Structure of the ATP-dependent oligomerization domain of N-ethylmaleimide sensitive factor complexed with ATP. Nature Struct. Biol. 5, 803–811 (1998).
    Article CAS Google Scholar
  15. Kay, B.K., Williamson, M.P. & Sudol, M. The importance of being proline: the interaction of proline-rich motifs in signaling proteins with their cognate domains. FASEB J. 14, 231–241 (2000).
    Article CAS Google Scholar
  16. Carter, T.C. & Gruneberg, H. Linkage between fidget and agouti in the house mouse. Heredity 4, 373–376 (1950).
    Article CAS Google Scholar
  17. Letts, V.A. et al. Genetic and physical maps of the stargazer locus on mouse Chromosome 15. Genomics 43, 62–68 (1997).
    Article CAS Google Scholar
  18. Cox, G.A., Mahaffey, C.L. & Frankel, W.N. Identification of the mouse neuromuscular degeneration gene and mapping of a second site suppressor allele. Neuron 21, 1327–1337 (1998).
    Article CAS Google Scholar
  19. Felsenstein, J. PHYLIP — Phylogeny Inference Package (Version 3.2). Cladistics 5, 164–166 (1989).
    Google Scholar
  20. Brown, N.L. et al. Math5 encodes a murine basic helix-loop-helix transcription factor expressed during early stages of retinal neurogenesis. Development 125, 4821–4833 (1998).
    CAS PubMed Google Scholar
  21. Kaufmann, M.H. The Atlas of Mouse Development (Academic, London, 1992).
    Google Scholar

Download references

Acknowledgements

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.).

Author information

Author notes

  1. Gregory A. Cox and Connie L. Mahaffey: These authors contributed equally to this work.

Authors and Affiliations

  1. The Jackson Laboratory, Bar Harbor, Maine, USA
    Gregory A. Cox, Connie L. Mahaffey, Arne Nystuen, Verity A. Letts & Wayne N. Frankel

Authors

  1. Gregory A. Cox
    You can also search for this author inPubMed Google Scholar
  2. Connie L. Mahaffey
    You can also search for this author inPubMed Google Scholar
  3. Arne Nystuen
    You can also search for this author inPubMed Google Scholar
  4. Verity A. Letts
    You can also search for this author inPubMed Google Scholar
  5. Wayne N. Frankel
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toWayne N. Frankel.

Rights and permissions

About this article

Cite this article

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). https://doi.org/10.1038/79923

Download citation