Gene Symbol: Neb
Description: nebulin
Alias: AI595938, nebulin
Species: mouse
Products:     Neb

Top Publications

  1. Fulop C, Kamath R, Li Y, Otto J, Salustri A, Olsen B, et al. Coding sequence, exon-intron structure and chromosomal localization of murine TNF-stimulated gene 6 that is specifically expressed by expanding cumulus cell-oocyte complexes. Gene. 1997;202:95-102 pubmed
  2. Taketo M, Parker K, Howard T, Tsukiyama T, Wong M, Niwa O, et al. Homologs of Drosophila Fushi-Tarazu factor 1 map to mouse chromosome 2 and human chromosome 9q33. Genomics. 1995;25:565-7 pubmed
    ..The mouse and human genes are located in the homologous regions of mouse Chr 2 and human Chr 9, respectively. ..
  3. Müller Seitz M, Kaupmann K, Labeit S, Jockusch H. Chromosomal localization of the mouse titin gene and its relation to "muscular dystrophy with myositis" and nebulin genes on chromosome 2. Genomics. 1993;18:559-61 pubmed
    In the mouse, the genes for the structural components of the myofibril titin and nebulin, Ttn and Neb, map to proximal Chr 2, as does the gene for a muscle disease, "muscular dystrophy with myositis," mdm...
  4. Kazmierski S, Antin P, Witt C, Huebner N, McElhinny A, Labeit S, et al. The complete mouse nebulin gene sequence and the identification of cardiac nebulin. J Mol Biol. 2003;328:835-46 pubmed
    b>Nebulin is a giant (M(r) 750-850kDa), modular sarcomeric protein proposed to regulate the assembly, and to specify the precise lengths of actin (thin) filaments in vertebrate skeletal muscles...
  5. Tonino P, Pappas C, Hudson B, Labeit S, Gregorio C, Granzier H. Reduced myofibrillar connectivity and increased Z-disk width in nebulin-deficient skeletal muscle. J Cell Sci. 2010;123:384-91 pubmed publisher
    ..studies in primary cultures of myocytes it has been proposed that desmin interacts with the sarcomeric protein nebulin. Here we tested whether nebulin is part of a novel biomechanical linker complex, by using a recently developed ..
  6. Witt C, Burkart C, Labeit D, McNabb M, Wu Y, Granzier H, et al. Nebulin regulates thin filament length, contractility, and Z-disk structure in vivo. EMBO J. 2006;25:3843-55 pubmed
    ..It has been hypothesized that nebulin, a giant filamentous protein extending along the entire length of the thin filament, provides a blueprint for ..
  7. Takano K, Watanabe Takano H, Suetsugu S, Kurita S, Tsujita K, Kimura S, et al. Nebulin and N-WASP cooperate to cause IGF-1-induced sarcomeric actin filament formation. Science. 2010;330:1536-40 pubmed publisher
    ..We found that IGF-1-induced phosphatidylinositol 3-kinase-Akt signaling formed a complex of nebulin and N-WASP at the Z bands of myofibrils by interfering with glycogen synthase kinase-3? in mice...
  8. Chandra M, Mamidi R, Ford S, Hidalgo C, Witt C, Ottenheijm C, et al. Nebulin alters cross-bridge cycling kinetics and increases thin filament activation: a novel mechanism for increasing tension and reducing tension cost. J Biol Chem. 2009;284:30889-96 pubmed publisher
    b>Nebulin is a giant filamentous F-actin-binding protein ( approximately 800 kDa) that binds along the thin filament of the skeletal muscle sarcomere. Nebulin is one of the least well understood major muscle proteins...
  9. Bang M, Caremani M, Brunello E, Littlefield R, Lieber R, Chen J, et al. Nebulin plays a direct role in promoting strong actin-myosin interactions. FASEB J. 2009;23:4117-25 pubmed publisher
    The role of the actin filament-associated protein nebulin on mechanical and kinetic properties of the actomyosin motor was investigated in skeletal muscle of wild-type (wt) and nebulin-deficient (nebulin(-)(/)(-)) mice that were 1 d old, ..

More Information


  1. Bang M, Li X, Littlefield R, Bremner S, Thor A, Knowlton K, et al. Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle. J Cell Biol. 2006;173:905-16 pubmed
    b>Nebulin is a giant modular sarcomeric protein that has been proposed to play critical roles in myofibrillogenesis, thin filament length regulation, and muscle contraction...
  2. Ottenheijm C, Witt C, Stienen G, Labeit S, Beggs A, Granzier H. Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency. Hum Mol Genet. 2009;18:2359-69 pubmed publisher
    ..Here, we studied the muscular phenotype of NM patients with a well-defined nebulin mutation (NM-NEB), using a multidisciplinary approach to study thin filament length regulation and muscle ..
  3. Gokhin D, Bang M, Zhang J, Chen J, Lieber R. Reduced thin filament length in nebulin-knockout skeletal muscle alters isometric contractile properties. Am J Physiol Cell Physiol. 2009;296:C1123-32 pubmed publisher
    b>Nebulin (NEB) is a large, rod-like protein believed to dictate actin thin filament length in skeletal muscle. NEB gene defects are associated with congenital nemaline myopathy...
  4. Malo D, Schurr E, Dorfman J, Canfield V, Levenson R, Gros P. Three brain sodium channel alpha-subunit genes are clustered on the proximal segment of mouse chromosome 2. Genomics. 1991;10:666-72 pubmed genes to the proximal segment of mouse chromosome 2 and suggested the probable gene order centromere-Hc-Neb-Pmv7-Scn2a/Scn3a-Scn1a-Mpmv 14...
  5. Braun T, Bober E, Rudnicki M, Jaenisch R, Arnold H. MyoD expression marks the onset of skeletal myogenesis in Myf-5 mutant mice. Development. 1994;120:3083-92 pubmed
    ..0 wild-type and mutant mice indicating that myogenic factor expression at the level of somites is not a prerequisite for determination and subsequent migration of limb precursor cells. ..
  6. Ottenheijm C, Buck D, De Winter J, Ferrara C, Piroddi N, Tesi C, et al. Deleting exon 55 from the nebulin gene induces severe muscle weakness in a mouse model for nemaline myopathy. Brain. 2013;136:1718-31 pubmed publisher
    b>Nebulin--a giant sarcomeric protein--plays a pivotal role in skeletal muscle contractility by specifying thin filament length and function...
  7. Lee E, De Winter J, Buck D, Jasper J, MALIK F, Labeit S, et al. Fast skeletal muscle troponin activation increases force of mouse fast skeletal muscle and ameliorates weakness due to nebulin-deficiency. PLoS ONE. 2013;8:e55861 pubmed publisher
    ..on calcium-induced force development was studied in skinned fast skeletal muscle fibers from wildtype (WT) and nebulin deficient (NEB KO) mice...
  8. Buck D, Hudson B, Ottenheijm C, Labeit S, Granzier H. Differential splicing of the large sarcomeric protein nebulin during skeletal muscle development. J Struct Biol. 2010;170:325-33 pubmed publisher
    We studied differential splicing of nebulin, a giant filamentous F-actin binding protein (M(r) approximately 700-800kDa) that is found in skeletal muscle...
  9. Schiaffino S, Reggiani C. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiol Rev. 1996;76:371-423 pubmed
    ..Additional isoforms, including products of tropomyosin, myosin light chain 1 fast, troponin T, titin, and nebulin genes, can be generated from the same gene through alternative splicing or use of alternative promoters...
  10. Li F, Buck D, De Winter J, Kolb J, Meng H, Birch C, et al. Nebulin deficiency in adult muscle causes sarcomere defects and muscle-type-dependent changes in trophicity: novel insights in nemaline myopathy. Hum Mol Genet. 2015;24:5219-33 pubmed publisher
    b>Nebulin is a giant filamentous protein that is coextensive with the actin filaments of the skeletal muscle sarcomere...
  11. Hughes D, Wallace M, Baar K. Effects of aging, exercise, and disease on force transfer in skeletal muscle. Am J Physiol Endocrinol Metab. 2015;309:E1-E10 pubmed publisher
  12. Joureau B, De Winter J, Stam K, Granzier H, Ottenheijm C. Muscle weakness in respiratory and peripheral skeletal muscles in a mouse model for nebulin-based nemaline myopathy. Neuromuscul Disord. 2017;27:83-89 pubmed publisher
    ..To investigate diaphragm contractility, in the present study we took advantage of a mouse model for nebulin-based nemaline myopathy that we recently developed...
  13. Rossi E, Faiella A, Zeviani M, Labeit S, Floridia G, Brunelli S, et al. Order of six loci at 2q24-q31 and orientation of the HOXD locus. Genomics. 1994;24:34-40 pubmed
    ..related to the Drosophila distal-less gene; and TTN and NEB, the genes for the two giant molecules titin and nebulin, both involved in the sarcomere structure, have been previously mapped to human 2q31-q32 and to mouse chromosome ..
  14. Zhang J, Luo G, Herrera A, Paterson B, Horowits R. cDNA cloning of mouse nebulin. Evidence that the nebulin-coding sequence is highly conserved among vertebrates. Eur J Biochem. 1996;239:835-41 pubmed
    b>Nebulin is a family of giant myofibrillar proteins with molecular masses ranging over 700-900 kDa. Using a human nebulin cDNA probe, we isolated three nebulin cDNA clones from a mouse skeletal muscle cDNA library...
  15. Kandli M, Feige E, Chen A, Kilfin G, Motro B. Isolation and characterization of two evolutionarily conserved murine kinases (Nek6 and nek7) related to the fungal mitotic regulator, NIMA. Genomics. 2000;68:187-96 pubmed
    ..Linkage analysis, using the murine BXD recombinant inbred strain panel, localized nek6 to chromosome 2 at 28 cM. Using a mouse/hamster radiation hybrid panel, we assigned the nek7 gene to chromosome 1 at approximately 73 cM. ..
  16. Nakagawa H, Suzuki H, Machida S, Suzuki J, Ohashi K, Jin M, et al. Contribution of the LIM domain and nebulin-repeats to the interaction of Lasp-2 with actin filaments and focal adhesions. PLoS ONE. 2009;4:e7530 pubmed publisher
    ..Lasp-2 has three structural regions: a LIM domain, a nebulin-repeat region, and an SH3 domain; however, the region(s) responsible for its interactions with actin filaments ..
  17. Qureshi S, Gros P, Letarte M, Malo D. The murine endoglin gene (Eng) maps to chromosome 2. Genomics. 1995;26:165-6 pubmed
  18. Mock B, Krall M, Blackwell J, O BRIEN A, Schurr E, Gros P, et al. A genetic map of mouse chromosome 1 near the Lsh-Ity-Bcg disease resistance locus. Genomics. 1990;7:57-64 pubmed
    ..7 +/- 0.8 cM) to the Lsh-Ity-Bcg locus. Two other DNA sequences, nebulin (Neb) and an anonymous DNA fragment (D2S3), which map to a region of human chromosome 2q that is homologous to ..
  19. Schurr E, Skamene E, Gros P. Mapping of the gene coding for the muscle protein nebulin (Neb) to the proximal region of mouse chromosome 2. Cytogenet Cell Genet. 1991;57:214-6 pubmed
    Using five different series of recombinant inbred (RI) strains, we have mapped the gene encoding nebulin, a muscle-specific protein...
  20. Gokhin D, Lewis R, McKeown C, Nowak R, Kim N, Littlefield R, et al. Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology. J Cell Biol. 2010;189:95-109 pubmed publisher
    ..Thus, Tmod3 and -4 compensate for the absence of Tmod1 structurally but not functionally. We conclude that Tmod1 is a novel regulator of skeletal muscle physiology. ..
  21. Ottenheijm C, Fong C, Vangheluwe P, Wuytack F, Babu G, Periasamy M, et al. Sarcoplasmic reticulum calcium uptake and speed of relaxation are depressed in nebulin-free skeletal muscle. FASEB J. 2008;22:2912-9 pubmed publisher
    Previous work suggested that altered Ca(2+) homeostasis might contribute to dysfunction of nebulin-free muscle, as gene expression analysis revealed that the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)-inhibitor sarcolipin (SLN) ..
  22. Braun T, Arnold H. Inactivation of Myf-6 and Myf-5 genes in mice leads to alterations in skeletal muscle development. EMBO J. 1995;14:1176-86 pubmed
    ..Our results provide evidence that skeletal myogenesis can proceed in the absence of two myogenic factors, Myf-5 and Myf-6, therefore they must exert largely non-redundant functions in vivo. ..
  23. Beckers M, Ernst E, Belcher S, Howe J, Levenson R, Gros P. A new sodium channel alpha-subunit gene (Scn9a) from Schwann cells maps to the Scn1a, Scn2a, Scn3a cluster of mouse chromosome 2. Genomics. 1996;36:202-5 pubmed
  24. Yamamoto D, Vitiello C, Zhang J, Gokhin D, Castaldi A, Coulis G, et al. The nebulin SH3 domain is dispensable for normal skeletal muscle structure but is required for effective active load bearing in mouse. J Cell Sci. 2013;126:5477-89 pubmed publisher
    ..It is caused by mutations in thin filament components, including nebulin, which accounts for about 50% of the cases...
  25. Ramirez Martinez A, Cenik B, Bezprozvannaya S, Chen B, Bassel Duby R, Liu N, et al. KLHL41 stabilizes skeletal muscle sarcomeres by nonproteolytic ubiquitination. elife. 2017;6: pubmed publisher that KLHL41 is poly-ubiquitinated and acts, at least in part, by preventing aggregation and degradation of Nebulin, an essential component of the sarcomere...
  26. Donner K, Nowak K, Aro M, Pelin K, Wallgren Pettersson C. Developmental and muscle-type-specific expression of mouse nebulin exons 127 and 128. Genomics. 2006;88:489-95 pubmed
    The human nebulin gene includes 183 exons and four regions of alternative splicing. The mouse nebulin gene, with 166 exons, has a similar organization...
  27. Klocke R, Augustin A, Ronsiek M, Stief A, van Der Putten H, Jockusch H. Dynamin genes Dnm1 and Dnm2 are located on proximal mouse chromosomes 2 and 9, respectively. Genomics. 1997;41:290-2 pubmed
    ..The nervous system-expressed gene Dnm1 was localized to Chr 2 between the genes for vimentin and nebulin, within a chromosomal region of conserved synteny to human chromosome 9q, consistent with the localization of the ..
  28. Askew D, Bartholomew C, Buchberg A, Valentine M, Jenkins N, Copeland N, et al. His-1 and His-2: identification and chromosomal mapping of two commonly rearranged sites of viral integration in a myeloid leukemia. Oncogene. 1991;6:2041-7 pubmed
    ..The His-1 locus maps to mouse chromosome 2 distinct from any known oncogene or common site of integration but near the proximal breakpoint for a deletion that is observed in over 90% of radiation-induced leukemias. ..
  29. Kaul A, Koster M, Neuhaus H, Braun T. Myf-5 revisited: loss of early myotome formation does not lead to a rib phenotype in homozygous Myf-5 mutant mice. Cell. 2000;102:17-9 pubmed
  30. Kolb J, Li F, Methawasin M, Adler M, Escobar Y, Nedrud J, et al. Thin filament length in the cardiac sarcomere varies with sarcomere length but is independent of titin and nebulin. J Mol Cell Cardiol. 2016;97:286-94 pubmed publisher
    ..Here we tested the previously proposed hypothesis that the actin-binding protein nebulin contributes to TFL regulation in the heart by using a cardiac-specific nebulin cKO mouse model (αMHC Cre Neb ..
  31. Li Z, Huang H, Boland P, Dominguez M, Burfeind P, Lai K, et al. Embryonic stem cell tumor model reveals role of vascular endothelial receptor tyrosine phosphatase in regulating Tie2 pathway in tumor angiogenesis. Proc Natl Acad Sci U S A. 2009;106:22399-404 pubmed publisher
    ..Endothelial differentiation in the ES teratoma model allows gene-targeting methods to be used in the study of tumor angiogenesis. ..
  32. Wu H, Hsu S, Wu W, Hu J, Ouyang P. Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin deficiency and elevated expression of slow-type muscle fiber genes. Biochem Biophys Res Commun. 2014;443:313-20 pubmed publisher
    ..In addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal muscle...
  33. Rouger K, Le Cunff M, Steenman M, Potier M, Gibelin N, Dechesne C, et al. Global/temporal gene expression in diaphragm and hindlimb muscles of dystrophin-deficient (mdx) mice. Am J Physiol Cell Physiol. 2002;283:C773-84 pubmed
    ..This finding should be taken under consideration for the interpretation of future experiments using mdx mice as a model for therapeutic assays. ..
  34. Ogut O, Hossain M, Jin J. Interactions between nebulin-like motifs and thin filament regulatory proteins. J Biol Chem. 2003;278:3089-97 pubmed
    b>Nebulin (600-900 kDa) and nebulette (107-109 kDa) are two homologous thin filament-associated proteins in skeletal and cardiac muscles, respectively...
  35. Garg A, O Rourke J, Long C, Doering J, Ravenscroft G, Bezprozvannaya S, et al. KLHL40 deficiency destabilizes thin filament proteins and promotes nemaline myopathy. J Clin Invest. 2014;124:3529-39 pubmed publisher
    ..We determined that KLHL40 localizes to the sarcomere I band and A band and binds to nebulin (NEB), a protein frequently implicated in NM, as well as a putative thin filament protein, leiomodin 3 (LMOD3)...
  36. Mastrototaro G, Liang X, Li X, Carullo P, Piroddi N, Tesi C, et al. Nebulette knockout mice have normal cardiac function, but show Z-line widening and up-regulation of cardiac stress markers. Cardiovasc Res. 2015;107:216-25 pubmed publisher
    ..These results suggest that the nebulette disease causing mutations have dominant gain-of-function effects. ..
  37. Hinze F, Dieterich C, Radke M, Granzier H, Gotthardt M. Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy. J Mol Med (Berl). 2016;94:1349-1358 pubmed
    ..Increasing the length of titin isoforms improves ventricular filling in heart disease. FHL proteins are regulated via RBM20 and adapt cardiac growth. RBM20 is a therapeutic target in diastolic dysfunction. ..
  38. Siracusa L, Alvord W, Bickmore W, Jenkins N, Copeland N. Interspecific backcross mice show sex-specific differences in allelic inheritance. Genetics. 1991;128:813-21 pubmed
    ..We now report the mapping of five loci (Actc-1, D2Hgu1, His-1, Hox-4.1 and Neb) to chromosome 2, which, in addition to the Abl, Ada, B2m, Bmp-2a, Hc, Emv-15, Fshb, Hck-1, Pax-1, Pck-1, Spna-2 ..
  39. Herrera A, Elzey B, Law D, Horowits R. Terminal regions of mouse nebulin: sequence analysis and complementary localization with N-RAP. Cell Motil Cytoskeleton. 2000;45:211-22 pubmed
    The regions of mouse nebulin extending from the ends of the super repeats to the C-terminus and N-terminus were cloned and sequenced...
  40. Miner J, Miller J, Wold B. Skeletal muscle phenotypes initiated by ectopic MyoD in transgenic mouse heart. Development. 1992;114:853-60 pubmed
  41. Bang M. Animal Models of Congenital Cardiomyopathies Associated With Mutations in Z-Line Proteins. J Cell Physiol. 2017;232:38-52 pubmed publisher
    ..Pros and cons of mouse models will be discussed and a future outlook will be given. J. Cell. Physiol. 232: 38-52, 2017. © 2016 Wiley Periodicals, Inc. ..