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Gene Review

Picalm  -  phosphatidylinositol binding clathrin...

Mus musculus

Synonyms: CALM, CLTH, Calm, Clathrin assembly lymphoid myeloid leukemia, Fit1, ...
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Disease relevance of Picalm

  • A variety of leukemias and lymphomas have been associated with translocations that fuse human PICALM with the putative transcription factor gene AF10 [1].
  • Furthermore, the Fti1 (fit-1) locus, a common integration site in feline leukaemia virus-induced T cell lymphomas, was mapped upstream of Mml3 [2].
  • The fit-1 locus was originally identified as a common insertion site for feline leukemia virus (FeLV) in thymic lymphosarcomas induced by FeLV-myc recombinant viruses, suggesting that it harbors a gene that cooperates with Myc in T-cell leukemogenesis [3].

High impact information on Picalm

  • These mutants thus provide unique models for exploring how the endocytic function of mouse Picalm and the transport processes mediated by clathrin and the AP2 complex contribute to normal hematopoiesis, iron metabolism, and growth [1].
  • We report that fit14R, as well as the most severe fit15R allele, are nonsense point mutations in the mouse ortholog of the human phosphatidylinositol-binding clathrin assembly protein (PICALM) gene, whose product is involved in clathrin-mediated endocytosis [1].
  • Complementation analysis provided evidence for a true repeat mutation at the sh-1 (shaker-1) locus (for the neurological mutations) and another at the here defined fit-1 (fitness-1) locus [4].
  • We report here that fit1 mutants are anemic, display numerous peripheral blood defects, and are deficient in early hematopoietic progenitor cell populations [5].
  • In this study, we show that polarized epithelial Madin-Darby canine kidney (MDCK) cells express two AP180-related proteins: the ubiquitously expressed 62-kDa clathrin assembly lymphoid myeloid leukemia (CALM, AP180-2) protein and a novel high-molecular-weight homolog that we have named AP180-3 [6].

Biological context of Picalm

  • The second, l7Rn6, is required for survival after birth. fit1, a third locus identified by chemical mutagenesis, maps distal to the eed interval and is also required for survival after birth [7].
  • Genetic and physical mapping of the fitness 1 (fit1) locus within the Fes-Hbb region of mouse chromosome 7 [8].

Associations of Picalm with chemical compounds

  • The fit1 locus, which is currently defined by five N-ethyl-N-nitrosourea (ENU)-induced mutations, was found to map in a subregion between the eed and exed loci [8].

Other interactions of Picalm

  • Positioning of fit1 between deletion breakpoints, and the isolation and mapping of a DNA probe proximal to it, should facilitate the cloning and molecular characterization of fit1, as well as of the eed locus and the tightly linked l(7)5Rn and l(7)6Rn loci [8].
  • This shows that fit-1 is located on mouse Chr 10, 1cM proximal to Ahi-1, a murine retroviral integration locus that is closely linked to Myb [3].


  1. Mutations in the clathrin-assembly gene Picalm are responsible for the hematopoietic and iron metabolism abnormalities in fit1 mice. Klebig, M.L., Wall, M.D., Potter, M.D., Rowe, E.L., Carpenter, D.A., Rinchik, E.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  2. Linkage on chromosome 10 of several murine retroviral integration loci associated with leukaemia. Haviernik, P., Festin, S.M., Opavsky, R., Koller, R.P., Barr, N.I., Neil, J.C., Wolff, L. J. Gen. Virol. (2002) [Pubmed]
  3. The fit-1 common integration locus in human and mouse is closely linked to MYB. Barr, N.I., Stewart, M., Tsatsanis, C., Fulton, R., Hu, M., Tsujimoto, H., Neil, J.C. Mamm. Genome (1999) [Pubmed]
  4. A strategy for fine-structure functional analysis of a 6- to 11-centimorgan region of mouse chromosome 7 by high-efficiency mutagenesis. Rinchik, E.M., Carpenter, D.A., Selby, P.B. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  5. Mutations in the murine fitness 1 gene result in defective hematopoiesis. Potter, M.D., Shinpock, S.G., Popp, R.A., Godfrey, V., Carpenter, D.A., Bernstein, A., Johnson, D.K., Rinchik, E.M. Blood (1997) [Pubmed]
  6. Potential role for a novel AP180-related protein during endocytosis in MDCK cells. Kusner, L., Carlin, C. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  7. Physical localization of eed: a region of mouse chromosome 7 required for gastrulation. Holdener, B.C., Thomas, J.W., Schumacher, A., Potter, M.D., Rinchik, E.M., Sharan, S.K., Magnuson, T. Genomics (1995) [Pubmed]
  8. Genetic and physical mapping of the fitness 1 (fit1) locus within the Fes-Hbb region of mouse chromosome 7. Potter, M.D., Klebig, M.L., Carpenter, D.A., Rinchik, E.M. Mamm. Genome (1995) [Pubmed]
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