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Gene Review

Pafah1b1  -  platelet-activating factor acetylhydrolase...

Mus musculus

Synonyms: LIS-1, Lis-1, Lis1, Lissencephaly-1 protein, MMS10-U, ...
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Disease relevance of Pafah1b1


Psychiatry related information on Pafah1b1


High impact information on Pafah1b1

  • Pafah1b1(+/-) mice have hippocampal layering defects, whereas homozygous mutants are embryonic lethal [5].
  • The phenotypes observed are distinct from those of other mouse mutants with neuronal migration defects, suggesting that Pafah1b1 participates in a novel pathway for neuronal migration [6].
  • Mice with further reduction of Pafah1b1 activity display more severe brain disorganization as well as cerebellar defects [6].
  • Our results demonstrate an essential, dosage-sensitive neuronal-specific role for Pafah1b1 in neuronal migration throughout the brain, and an essential role in early embryonic development [6].
  • Recently, we and others reported that the doublecortin gene is responsible for X-linked lissencephaly and subcortical laminar heterotopia [7].

Biological context of Pafah1b1


Anatomical context of Pafah1b1

  • Rescue of these defects in mouse embryonic fibroblasts and granule cells by overexpressing LIS1, NDEL1, or NDE1 suggest that NDEL1, LIS1, and NDE1 act in a common pathway to regulate dynein but each has distinct roles in the regulation of microtubule organization and neuronal migration [12].
  • Disregulated RhoGTPases and actin cytoskeleton contribute to the migration defect in Lis1-deficient neurons [13].
  • Lis1 is necessary for normal non-radial migration of inhibitory interneurons [4].
  • We have generated a mouse mutant (LIS1GT/GT) by gene trap integration leading to selective disruption of a Lis1 splicing variant in testis [2].
  • These results provide evidence for an essential and hitherto uncharacterized role of the Lis1 protein in spermatogenesis, particularly in the differentiation of spermatids into spermatozoa [2].

Associations of Pafah1b1 with chemical compounds

  • The deletion resulted in a shorter protein (sLIS1) that initiates from the second methionine, a unique situation because most LIS1 mutations result in a null allele [14].
  • With the lithium diiodosalicylate (LIS1) extraction-phenol partition method, we have isolated a sialoglycoprotein fraction from DBA/2 mouse erythrocyte ghosts [15].

Regulatory relationships of Pafah1b1

  • These data indicate a previously unrecognized role for Lis1 protein in neuronal motility by promoting actin polymerization through the regulation of Rho GTPase activity [13].

Other interactions of Pafah1b1

  • Our results indicate that, in hippocampal neurons, MAP1B and LIS1 co-localize, associate and interact with each another [16].
  • Regulation of cytoplasmic dynein ATPase by Lis1 [10].
  • We now find that dynein and its regulators dynactin and LIS1 localize to the leading cell cortex during this process [11].
  • We have examined the effect of disorganisation of the mitral cell soma layer in mutant mice heterozygous for the beta-subunit of platelet activating factor acetylhydrolase (Lis1(-/+)) on the targeting of primary olfactory axons [17].
  • Integrin-linked kinase deletion from mouse cortex results in cortical lamination defects resembling cobblestone lissencephaly [18].

Analytical, diagnostic and therapeutic context of Pafah1b1


  1. Mitotic spindle regulation by Nde1 controls cerebral cortical size. Feng, Y., Walsh, C.A. Neuron (2004) [Pubmed]
  2. Inactivation of a testis-specific Lis1 transcript in mice prevents spermatid differentiation and causes male infertility. Nayernia, K., Vauti, F., Meinhardt, A., Cadenas, C., Schweyer, S., Meyer, B.I., Schwandt, I., Chowdhury, K., Engel, W., Arnold, H.H. J. Biol. Chem. (2003) [Pubmed]
  3. FAK deficiency in cells contributing to the basal lamina results in cortical abnormalities resembling congenital muscular dystrophies. Beggs, H.E., Schahin-Reed, D., Zang, K., Goebbels, S., Nave, K.A., Gorski, J., Jones, K.R., Sretavan, D., Reichardt, L.F. Neuron (2003) [Pubmed]
  4. Lis1 is necessary for normal non-radial migration of inhibitory interneurons. McManus, M.F., Nasrallah, I.M., Pancoast, M.M., Wynshaw-Boris, A., Golden, J.A. Am. J. Pathol. (2004) [Pubmed]
  5. Interaction of reelin signaling and Lis1 in brain development. Assadi, A.H., Zhang, G., Beffert, U., McNeil, R.S., Renfro, A.L., Niu, S., Quattrocchi, C.C., Antalffy, B.A., Sheldon, M., Armstrong, D.D., Wynshaw-Boris, A., Herz, J., D'Arcangelo, G., Clark, G.D. Nat. Genet. (2003) [Pubmed]
  6. Graded reduction of Pafah1b1 (Lis1) activity results in neuronal migration defects and early embryonic lethality. Hirotsune, S., Fleck, M.W., Gambello, M.J., Bix, G.J., Chen, A., Clark, G.D., Ledbetter, D.H., McBain, C.J., Wynshaw-Boris, A. Nat. Genet. (1998) [Pubmed]
  7. Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Francis, F., Koulakoff, A., Boucher, D., Chafey, P., Schaar, B., Vinet, M.C., Friocourt, G., McDonnell, N., Reiner, O., Kahn, A., McConnell, S.K., Berwald-Netter, Y., Denoulet, P., Chelly, J. Neuron (1999) [Pubmed]
  8. Previously uncharacterized roles of platelet-activating factor acetylhydrolase 1b complex in mouse spermatogenesis. Yan, W., Assadi, A.H., Wynshaw-Boris, A., Eichele, G., Matzuk, M.M., Clark, G.D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  9. Characterization and chromosomal mapping of two pseudogenes of the mouse Pafaha/Lis1 gene: retrointegration hotspots in the mouse genome. Péterfy, M., Gyuris, T., Antonio, L., Takács, L. Gene (1998) [Pubmed]
  10. Regulation of cytoplasmic dynein ATPase by Lis1. Mesngon, M.T., Tarricone, C., Hebbar, S., Guillotte, A.M., Schmitt, E.W., Lanier, L., Musacchio, A., King, S.J., Smith, D.S. J. Neurosci. (2006) [Pubmed]
  11. A role for cytoplasmic dynein and LIS1 in directed cell movement. Dujardin, D.L., Barnhart, L.E., Stehman, S.A., Gomes, E.R., Gundersen, G.G., Vallee, R.B. J. Cell Biol. (2003) [Pubmed]
  12. Complete loss of Ndel1 results in neuronal migration defects and early embryonic lethality. Sasaki, S., Mori, D., Toyo-oka, K., Chen, A., Garrett-Beal, L., Muramatsu, M., Miyagawa, S., Hiraiwa, N., Yoshiki, A., Wynshaw-Boris, A., Hirotsune, S. Mol. Cell. Biol. (2005) [Pubmed]
  13. Disregulated RhoGTPases and actin cytoskeleton contribute to the migration defect in Lis1-deficient neurons. Kholmanskikh, S.S., Dobrin, J.S., Wynshaw-Boris, A., Letourneau, P.C., Ross, M.E. J. Neurosci. (2003) [Pubmed]
  14. Targeted mutagenesis of Lis1 disrupts cortical development and LIS1 homodimerization. Cahana, A., Escamez, T., Nowakowski, R.S., Hayes, N.L., Giacobini, M., von Holst, A., Shmueli, O., Sapir, T., McConnell, S.K., Wurst, W., Martinez, S., Reiner, O. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  15. Isolation and partial characterization of the sialoglycoprotein fraction of murine erythrocyte ghosts. Sarris, A.H., Palade, G.E. J. Cell Biol. (1982) [Pubmed]
  16. Binding of microtubule-associated protein 1B to LIS1 affects the interaction between dynein and LIS1. Jiménez-Mateos, E.M., Wandosell, F., Reiner, O., Avila, J., González-Billault, C. Biochem. J. (2005) [Pubmed]
  17. Laminar disorganisation of mitral cells in the olfactory bulb does not affect topographic targeting of primary olfactory axons. Royal, S.J., Gambello, M.J., Wynshaw-Boris, A., Key, B., Clarris, H.J. Brain Res. (2002) [Pubmed]
  18. Integrin-linked kinase deletion from mouse cortex results in cortical lamination defects resembling cobblestone lissencephaly. Niewmierzycka, A., Mills, J., St-Arnaud, R., Dedhar, S., Reichardt, L.F. J. Neurosci. (2005) [Pubmed]
  19. Cloning and characterization of cDNAs and the gene encoding the mouse platelet-activating factor acetylhydrolase Ib alpha subunit/lissencephaly-1 protein. Péterfy, M., Gyuris, T., Grosshans, D., Cuaresma, C.C., Takács, L. Genomics (1998) [Pubmed]
  20. A study of the nature of embryonic lethality in LIS1-/- mice. Cahana, A., Jin, X.L., Reiner, O., Wynshaw-Boris, A., O'Neill, C. Mol. Reprod. Dev. (2003) [Pubmed]
  21. Localization of the mouse lissencephaly-1 gene to mouse chromosome 11B3, in close proximity to D11Mit65. Péterfy, M., Hozier, J.C., Hall, B., Gyuris, T., Péterfy, K., Takécs, L. Somat. Cell Mol. Genet. (1995) [Pubmed]
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