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Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death
Abstract
The gene FUS (also known as TLS (for translocated in liposarcoma) and hnRNP P2) is translocated with the gene encoding the transcription factor ERG-1 in human myeloid leukaemias. Although the functions of wild-type FUS are unknown, the protein contains an RNA-recognition motif and is a component of nuclear riboprotein complexes. FUS resembles a transcription factor in that it binds DNA, contributes a transcriptional activation domain to the FUS-ERG oncoprotein and interacts with several transcription factors in vitro. To better understand FUS function in vivo, we examined the consequences of disrupting Fus in mice. Our results indicate that Fus is essential for viability of neonatal animals, influences lymphocyte development in a non-cell-intrinsic manner, has an intrinsic role in the proliferative responses of B cells to specific mitogenic stimuli and is required for the maintenance of genomic stability. The involvement of a nuclear riboprotein in these processes in vivo indicates that Fus is important in genome maintenance.
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“Fus-null mice die soon after birth179”
From The neurogenetics of alternative splicing (2016) · cites this paper as [179]
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Schreiber, E. H., Matthias, P., Müller, M. M., & Schaffner, W. (1989) · Nucleic Acids Research · doi:10.1093/nar/17.15.6419 · Cited by 4,179
Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia
Barlow, C., Hirotsune, S., Paylor, R. E., Liyanage, M., Eckhaus, M., Collins, F. S., Shiloh, Y., Crawley, J. N., Ried, T., Tagle, D. A., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)80086-0 · Cited by 1,465
Xu, Y., Ashley, T., Brainerd, E. E., Bronson, R. T., Meyn, M. S., & Baltimore, D. (1996) · Genes & Development · doi:10.1101/gad.10.19.2411 · Cited by 830
Baskaran, R., Wood, L. D., Whitaker, L. L., Canman, C. E., Morgan, S. E., Xu, Y., Barlow, C., Baltimore, D., Wynshaw-Boris, A. J., Kastan, M. B., et al. (1997) · Nature · doi:10.1038/387516a0 · Cited by 538
Interaction between ATM protein and c-Abl in response to DNA damage
Shafman, T. D., Khanna, K. K., Kedar, P. S., Spring, K. J., Kozlov, S., Yen, T. J., Hobson, K., Gatei, M. H., Zhang, N., Watters, D. J., et al. (1997) · Nature · doi:10.1038/387520a0 · Cited by 478
Dual roles of ATM in the cellular response to radiation and in cell growth control.Preprint
Xu, Y., & Baltimore, D. (1996) · Genes & Development · doi:10.1101/gad.10.19.2401 · Cited by 407
Singh, N., Hong, S., Scherer, D. C., Serizawa, I., Burdin, N., Kronenberg, M., Koezuka, Y., & Kaer, L. V. (1999) · PubMed · Cited by 358
Self-citationTransitional B cells are the target of negative selection in the B cell compartment.
Carsetti, R., Köhler, G., & Lamers, M. C. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.6.2129 · Cited by 358
A human RNA polymerase II complex associated with SRB and DNA-repair proteins
Maldonado, E., Shiekhattar, R., Sheldon, M., Cho, H. K., Drapkin, R., Rickert, P., Lees, E. M., Anderson, C. W., Linn, S., & Reinberg, D. (1996) · Nature · doi:10.1038/381086a0 · Cited by 351
Schwartzberg, P. L., Stall, A. M., Hardin, J. D., Bowdish, K. S., Humaran, T. J., Boast, S., Harbison, M. L., Robertson, E. J., & Goff, S. P. (1991) · Cell · doi:10.1016/0092-8674(91)90012-n · Cited by 351
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Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis
Kwiatkowski, T. J., Bosco, D. A., LeClerc, A. L., Tamrazian, E., Vanderburg, C. R., Russ, C., Davis, A., Gilchrist, J. M., Kasarskis, E. J., Munsat, T. L., et al. (2009) · Science · doi:10.1126/science.1166066 · Cited by 2,624
Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis
Ling, S.-C., Polymenidou, M., & Cleveland, D. W. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.033 · Cited by 1,811
“Two independent FUS/TLS knockout mouse models have been generated (Kuroda et al., 2000; Hicks et al., 2000).”
TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration
Lagier-Tourenne, C., Polymenidou, M., & Cleveland, D. W. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq137 · Cited by 1,021
Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription
Wang, X., Arai, S., Song, X., Reichart, D. R., Du, K., Pascual, G., Tempst, P., Rosenfeld, M. G., Glass, C. K., & Kurokawa, R. (2008) · Nature · doi:10.1038/nature06992 · Cited by 1,007
“S5b), while the N-terminus (1-211) interacted with CBP (Fig.”
BackgroundTDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia
Mackenzie, I. R., Rademakers, R., & Neumann, M. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70195-2 · Cited by 1,012
The changing scene of amyotrophic lateral sclerosis
Robberecht, W., & Philips, T. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3430 · Cited by 957
Stress granules as crucibles of ALS pathogenesis
Li, Y. R., King, O. D., Shorter, J., & Gitler, A. D. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201302044 · Cited by 948
“Significant cellular damage and death is induced by TDP43 or FUS knockdown in neurons, primary cell lines, and model organisms, which suggests a loss-of-function (LOF) model (Hicks et al., 2000; Ayala et al., 2008a).”
BackgroundDivergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs
Lagier‐Tourenne, C., Polymenidou, M., Hutt, K. R., Vu, A. Q., Baughn, M. W., Huelga, S. C., Clutario, K. M., Ling, S., Liang, T. Y., Mazur, C., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3230 · Cited by 769
Self-citationA new subtype of frontotemporal lobar degeneration with FUS pathology
Neumann, M., Rademakers, R., Roeber, S., Baker, M., Kretzschmar, H. A., & Mackenzie, I. R. A. (2009) · Brain · doi:10.1093/brain/awp214 · Cited by 722
“FUS knock-out mice show perinatal mortality (Hicks et al., 2000).”
DNA damage and its links to neurodegeneration
Madabhushi, R., Pan, L., & Tsai, L.-H. (2014) · Neuron · doi:10.1016/j.neuron.2014.06.034 · Cited by 654
“mice suffer from high levels of genomic instability, defective B-lymphocyte development, male sterility, and undergo perinatal death, and FUS was shown to participate in D-loop formation, which is an intermediate step in DNA repair through HR (Baechtold et al., 1999; Hicks et al., 2000; Kuroda et al., 2000).”
Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose)
Altmeyer, M., Neelsen, K. J., Teloni, F., Pozdnyakova, I., Pellegrino, S., Grøfte, M., Rask, M., Streicher, W. W., Jungmichel, S., Nielsen, M. L., et al. (2015) · Nature Communications · doi:10.1038/ncomms9088 · Cited by 581
Protein aggregation in amyotrophic lateral sclerosis
Blokhuis, A. M., Groen, E. J. N., Koppers, M., van den Berg, L. H., & Pasterkamp, R. J. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1125-6 · Cited by 607
“43 results in premature death in mice [81, 112, 115, 172].”
BackgroundFUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons
Errichelli, L., Modigliani, S. D., Laneve, P., Colantoni, A., Legnini, I., Capauto, D., Rosa, A., Santis, R. D., Scarfò, R., Peruzzi, G., et al. (2017) · Nature Communications · doi:10.1038/ncomms14741 · Cited by 548
“Mouse embryonic stem cells (mESCs), derived from wild-type ( FUS þ / þ ) or knock out ( FUS (cid:2) / (cid:2) ) 38 FUS mice and expressing a green fluorescent protein (GFP) reporter under the control of the MN-specific Hb9 promoter ( Hb9::GFP transgene) 39 , were differentiated into bona fide MNs…”
Functional diversity of the hnRNPs: past, present and perspectives
Han, S. P., Tang, Y., & Smith, R. (2010) · Biochemical Journal · doi:10.1042/bj20100396 · Cited by 527
Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons
Wang, W., Pan, L., Su, S. C., Quinn, E. J., Sasaki, M., Jimenez, J., Mackenzie, I. R., Huang, E. J., & Tsai, L. (2013) · Nature Neuroscience · doi:10.1038/nn.3514 · Cited by 467
ALS Genetics: Gains, Losses, and Implications for Future Therapies
Kim, G., Gautier, O., Tassoni-Tsuchida, E., Ma, X. R., & Gitler, A. D. (2020) · Neuron · doi:10.1016/j.neuron.2020.08.022 · Cited by 370
“, 2000), whereas global Fus knockout causes perinatal death in inbred C57BL/6 mice (Hicks et al., 2000).”
BackgroundPhysiological functions and pathobiology of TDP ‐43 and FUS / TLS proteins
Ratti, A., & Buratti, E. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13625 · Cited by 417
The role of FUS gene variants in neurodegenerative diseases
Deng, H., Gao, K., & Jankovic, J. J. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.78 · Cited by 371
A Proteomic Analysis of Arginine-methylated Protein Complexes
Boisvert, F., Côté, J., Boulanger, M., & Richard, S. (2003) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m300088-mcp200 · Cited by 357
“The TLS protein has been shown to function as a splicing factor and is also implicated in DNA repair (44, 45).”
BackgroundDeng, H., Zhai, H., Bigio, E. H., Yan, J., Fecto, F., Ajroud, K., Mishra, M., Ajroud‐Driss, S., Heller, S., Sufit, R. L., et al. (2010) · Annals of Neurology · doi:10.1002/ana.22051 · Cited by 363
Understanding the role of TDP-43 and FUS/TLS in ALS and beyond
Da Cruz, S., & Cleveland, D. W. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.05.029 · Cited by 351
The neurogenetics of alternative splicing
Vuong, C. K., Black, D. L., & Zheng, S. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.27 · Cited by 340
Biology of EWS/ETS fusions in Ewing's family tumors
Arvand, A., & Denny, C. T. (2001) · Oncogene · doi:10.1038/sj.onc.1204598 · Cited by 350
“On a developmental level, TLS has been successfully knocked out in the mouse by two independent groups and the resulting phenotypes have been surprising (Hicks et al., 2000; Kuroda et al., 2000).”
BackgroundAndersson, M. K., Ståhlberg, A., Arvidsson, Y., Olofsson, A., Semb, H., Stenman, G., Nilsson, O., & Åman, P. (2008) · BMC Cell Biology · doi:10.1186/1471-2121-9-37 · Cited by 354
“Furthermore, FUS and EWS have been shown to be required for B lymphocyte development and for spermatogenesis in mice [38-40].”
ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function
Sharma, A., Lyashchenko, A. K., Lü, L., Nasrabady, S. E., Elmaleh, M., Mendelsohn, M. M., Nemes, A., Tapia, J. C., Mentis, G. Z., & Shneider, N. A. (2016) · Nature Communications · doi:10.1038/ncomms10465 · Cited by 351
Structural, super-resolution microscopy analysis of paraspeckle nuclear body organization
West, J. A., Mito, M., Kurosaka, S., Takumi, T., Tanegashima, C., Chujo, T., Yanaka, K., Kingston, R. E., Hirose, T., Bond, C. S., et al. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201601071 · Cited by 338
“We thus investigated the structures formed by Neat1_2 using mouse embryonic fibroblast (MEF) cells prepared from Fus KO mice (Hicks et al., 2000), which exhibit neonatal lethality caused by genomic instability.”
BackgroundMethodInfluentialFujii, R., Okabe, S., Urushido, T., Inoue, K., Yoshimura, A., Tachibana, T., Nishikawa, T., Hicks, G. G., & Takumi, T. (2005) · Current Biology · doi:10.1016/j.cub.2005.01.058 · Cited by 322
Self-citationVirtaneva, K. I., Wright, F. A., Tanner, S. M., Yuan, B., Lemon, W. J., Caligiuri, M. A., Bloomfield, C. D., de la Chapelle, A., & Krahe, R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.3.1124 · Cited by 311
Mitchell, J. C., McGoldrick, P., Vance, C. A., Hortobágyi, T., Sreedharan, J., Rogelj, B., Tudor, E. L., Smith, B. N., Klasen, C., Miller, C. C. J., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1043-z · Cited by 308
“chromosomal instability and perinatal death [20], but only causes male sterility and enhanced sensitivity to radiation”
BackgroundRiggi, N., & Stamenkovic, I. (2007) · Cancer Letters · doi:10.1016/j.canlet.2006.12.009 · Cited by 301
Widespread binding of FUS along nascent RNA regulates alternative splicing in the brain
Rogelj, B., Easton, L. E., Bogu, G. K., Stanton, L. W., Rot, G., Curk, T., Zupan, B., Sugimoto, Y., Modic, M., Haberman, N., et al. (2012) · Scientific Reports · doi:10.1038/srep00603 · Cited by 278
Korben, V. A., Lyashchenko, A. K., Blanco-Redondo, B., Jafar‐Nejad, P., & Shneider, N. A. (2022) · Nature Medicine · doi:10.1038/s41591-021-01615-z · Cited by 277
“FUS plays a critical role in development, as shown by the perinatal lethality of the elimination of FUS in knockout mice (KO/KO) 24 .”
Naumann, M., Pal, A., Goswami, A., Lojewski, X., Japtok, J., Vehlow, A., Naujock, M., Günther, R., Jin, M., Stanslowsky, N., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02299-1 · Cited by 275
ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects
Qiu, H., Lee, S., Shang, Y., Wang, W., Au, K. F., Kamiya, S., Barmada, S. J., Finkbeiner, S. M., Lui, H., Carlton, C. E., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci72723 · Cited by 284
“Previous studies have shown that WT FUS proteins are required for DNA damage repair (5, 6).”
The TET Family of Proteins: Functions and Roles in Disease
Tan, A. Y., & Manley, J. L. (2009) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjp025 · Cited by 282
“In an animal model, TLS knockout mice have high genomic instability due to chromosomal pairing defects and enhanced sensitivity to radiation (Hicks et al., 2000; Kuroda et al., 2000).”
BackgroundMastrocola, A. S., Kim, S. H., Trinh, A. T., Rodenkirch, L. A., & Tibbetts, R. S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.497974 · Cited by 280
“Cellular extracts from FUS / testes are unable to promote pairing between homologous DNA sequences in vitro (41), and FUS was shown to promote D-loop formation (34), an essential step in the repair of DSBs through theHR pathway (42).”
BackgroundResultInfluentialFUS/ERG gene fusions in Ewing's tumors.
Shing, D. C., McMullan, D. J., Roberts, P., Smith, K. K., Chin, S., Nicholson, J. C., Tillman, R. M., Ramani, P., Cullinane, C., & Coleman, N. (2003) · PubMed · Cited by 265
TLS facilitates transport of mRNA encoding an actin-stabilizing protein to dendritic spines
Fujii, R., & Takumi, T. (2005) · Journal of Cell Science · doi:10.1242/jcs.02692 · Cited by 253
Scekic‐Zahirovic, J., Sendscheid, O., Oussini, H. E., Jambeau, M., Sun, Y., Mersmann, S., Wagner, M., Dieterle, S., Sinniger, J., Dirrig‐Grosch, S., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201592559 · Cited by 262
“…microarrays in striatum from adult wild-type mice with antisense oligonucleotide-mediated depletion of Fus (Lagier-Tourenne et al , 2012), or in embryonic brains from another Fus knockout model that expresses low levels of truncated FUS protein (Hicks et al , 2000; Lagier-Tourenne et al , 2012).”
López‐Erauskin, J., Tadokoro, T., Baughn, M. W., Myers, B., McAlonis‐Downes, M., Chillón-Marinas, C., Asiaban, J. N., Artates, J. W., Bui, A. T., Vetto, A. P., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.09.044 · Cited by 233
“, 2015) or deletion (Hicks et al., 2000) of Fus inmouse hippocampal neurons causes abnormal spine morphology and density, consistent with a role for FUS in modulation of neuronal plasticity or synaptic activity—potentially through the alteration of mRNA stability (Udagawaet al.”
BackgroundSelf-citationBiochemical Properties and Biological Functions of FET Proteins
Schwartz, J. C., Cech, T. R., & Parker, R. (2014) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-034325 · Cited by 236
Genetic mutations in RNA-binding proteins and their roles in ALS
Kapeli, K., Martinez, F. J., & Yeo, G. W.-M. (2017) · Human Genetics · doi:10.1007/s00439-017-1830-7 · Cited by 225
“2017) while complete loss of FUS or EWSR1 in mice is postnatal lethal (Hicks et al. 2000; Li et al. 2007).”
BackgroundGao, F., Almeida, S., & Lopez‐Gonzalez, R. (2017) · The EMBO Journal · doi:10.15252/embj.201797568 · Cited by 227
“Indeed, FUS -deficient fibroblasts from knockout mice have increased sensitivity to ionizing irradiation along with chromosome abnormalities, such as chromosome breakage, centromeric fusion, and aneuploidy (Hicks et al , 2000; Kuroda et al , 2000).”
ALS-Associated FUS Mutations Result in Compromised FUS Alternative Splicing and Autoregulation
Zhou, Y., Liu, S., Liu, G., Öztürk, A., & Hicks, G. G. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003895 · Cited by 223
“For example, loss of FUS can cause genomic instability and developmental defects in mouse, Drosophila and Zebrafish [18,19,53].”
BackgroundSelf-citationFUS-dependent liquid–liquid phase separation is important for DNA repair initiation
Levone, B. R., Lenzken, S. C., Antonaci, M., Maiser, A., Rapp, A. W., Conte, F., Reber, S., Mechtersheimer, J., Ronchi, A. E., Mühlemann, O., et al. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202008030 · Cited by 220
“Mice lacking FUS are hypersensitive to ionizing radiation and show defects in spermatogenesis and chromosomal instability (Hicks et al., 2000; Kuroda et al., 2000).”
Frameshift and novel mutations in FUS in familial amyotrophic lateral sclerosis and ALS/dementia
Yan, J., Deng, H., Siddique, N. A., Fecto, F., Chen, W., Yang, Y., Liu, E., Donkervoort, S. C., Zheng, J. G., Shi, Y., et al. (2010) · Neurology · doi:10.1212/wnl.0b013e3181f07e0c · Cited by 218
Huang, C., Zhou, H., Tong, J., Chen, H., Liu, Y., Wang, D., Wei, X., & Xia, X. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002011 · Cited by 224
“Deletion of the fus gene results in chromosomal instability and perinatal death in inbred mice [24], but causes only male sterility in outbred mice [25].”
BackgroundTLS, EWS and TAF15: a model for transcriptional integration of gene expression
Law, W. J. (2006) · Briefings in Functional Genomics and Proteomics · doi:10.1093/bfgp/ell015 · Cited by 203
“TLS-deficient mice and showed that TLS, among its other functions, is required for genomic stability [36].”
BackgroundRulten, S. L., Rotheray, A., Green, R. L., Grundy, G. J., Moore, D. A. Q., Gómez-Herreros, F., Hafezparast, M., & Caldecott, K. W. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt835 · Cited by 190
“Consistent with this notion, FUS is phosphorylated by ATM (44), FUS / mice exhibit chromosomal instability and radiosensitivity (45,46), and Mastrocola et al.”
BackgroundIdentification of an RNA Binding Specificity for the Potential Splicing Factor TLS
Lerga, A., Hallier, M., Delva, L., Orvain, C., Gallais, I., Marie, J., & Moreau-Gachelin, F. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008304200 · Cited by 193
EWS–ETS oncoproteins: The linchpins of Ewing tumors
Janknecht, R. (2005) · Gene · doi:10.1016/j.gene.2005.08.007 · Cited by 173
Lu, Z. H., Books, J. T., & Ley, T. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.11.4625-4637.2005 · Cited by 181
“The loss of murine Fus/TLS, a YB-1-interacting multifunctional ribonucleoprotein, has been shown to cause chromosomal instability and perinatal death (16).”
BackgroundTDP ‐43 and FUS en route from the nucleus to the cytoplasm
Ederle, H., & Dormann, D. (2017) · FEBS Letters · doi:10.1002/1873-3468.12646 · Cited by 172
FUS is Phosphorylated by DNA-PK and Accumulates in the Cytoplasm after DNA Damage
Deng, Q., Holler, C. J., Taylor, G., Hudson, K. F., Watkins, W., Gearing, M., Ito, D., Murray, M. E., Dickson, D. W., Seyfried, N. T., et al. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0172-14.2014 · Cited by 161
“Furthermore, FUS knock-out mice have genomic instability, increased sensitivity to radiation, and evidence of impaired DNA repair (Hicks et al., 2000; Kuroda et al., 2000).”
BackgroundNomura, T., Watanabe, S., Kaneko, K., Yamanaka, K., Nukina, N., & Furukawa, Y. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.516492 · Cited by 160
Carey, J. L., & Guo, L. E. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.826719 · Cited by 166
“FUS involvement in DNA damage repair was first suggested when defects in the repair of DNA damage produced by ionizing radiation in FUS knockout mice was observed (Baechtold et al., 1999; Hicks et al., 2000; Kuroda et al., 2000).”
BackgroundRodent models of amyotrophic lateral sclerosis
McGoldrick, P., Joyce, P. I., Fisher, E., & Greensmith, L. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.03.012 · Cited by 162
Mechanisms of FUS mutations in familial amyotrophic lateral sclerosis
Shang, Y., & Huang, E. J. (2016) · Brain Research · doi:10.1016/j.brainres.2016.03.036 · Cited by 164
“Consequently, FUS–/– mice present with increased numbers of unpaired and mispaired chromosomal axes in pre-meiotic spermatocytes and in B lymphocytes (Hicks et al., 2000; Kuroda et al., 2000).”
InfluentialYasui, W., Oue, N., Ito, R., Kuraoka, K., & Nakayama, H. (2004) · Cancer Science · doi:10.1111/j.1349-7006.2004.tb03220.x · Cited by 152
De novo truncating FUS gene mutation as a cause of sporadic amyotrophic lateral sclerosis
DeJesus‐Hernandez, M., Kocerha, J., Finch, N. A., Crook, R., Baker, M. C., Desaro, P., Johnston, A., Rutherford, N. J., Wojtas, A., Kennelly, K. D., et al. (2010) · Human Mutation · doi:10.1002/humu.21241 · Cited by 158
Sarcomas: genetics, signalling, and cellular origins. Part 1: The fellowship of TET
Riggi, N., Cironi, L., Suvà, M., & Stamenkovic, I. (2007) · The Journal of Pathology · doi:10.1002/path.2209 · Cited by 154
“The Bcell defect is different from that in EWSR1−/− mice in that it is non-cell autonomous, as demonstrated by reconstitution experiments in which B cells were fully reconstituted by the FUS−/− donor cells [163].”
BackgroundEwing sarcoma gene EWS is essential for meiosis and B lymphocyte development
Li, K., Watford, W. T., Li, C., Parmelee, A., Bryant, M., Deng, C., O’Shea, J. J., & Lee, S. B. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31222 · Cited by 146
“Similarly, Tls–/– mice are also radiosensitive (47), and Tls–/– MEFs display genomic instability (46).”
BackgroundFrom animal models to human disease: a genetic approach for personalized medicine in ALS
Picher‐Martel, V., Valdmanis, P. N., Gould, P. V., Julien, J., & Dupré, N. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0340-5 · Cited by 163
Roles for RNA-binding proteins in development and disease
Brinegar, A. E., & Cooper, T. A. (2016) · Brain Research · doi:10.1016/j.brainres.2016.02.050 · Cited by 153
“Homozygous knockout of Fus produces perinatal lethality in inbred mouse lines (Hicks et al., 2000).”
Kino, Y., Washizu, C., Aquilanti, E., Okuno, M., Kurosawa, M., Yamada, M., Doi, H., & Nukina, N. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1162 · Cited by 149
“To date, two independent TLS knockout mouse strains were established (23,24).”
BackgroundTDP-43/FUS in motor neuron disease: Complexity and challenges
Guerrero, E. N., Wang, H., Mitra, J., Hegde, P. M., Stowell, S. E., Liachko, N. F., Kraemer, B. C., Garruto, R. M., Rao, K. S. J., & Hegde, M. L. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.09.004 · Cited by 146
“Both mice lines have high genomic instability (Hicks et al, 2000; Kuroda et al, 2000).”
BackgroundFused in sarcoma (FUS): An oncogene goes awry in neurodegeneration
Dormann, D., & Haass, C. (2013) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2013.03.006 · Cited by 140
“Consistently, FUS and EWS knockout mice show enhanced radiation sensitivity, defects in B cell development and spermatogenesis as well as genomic instability (Hicks et al., 2000; Kuroda et al., 2000; Li et al., 2007).”
BackgroundDr. Jekyll and Mr. Hyde: The Two Faces of the FUS/EWS/TAF15 Protein Family
Kovar, H. (2010) · Sarcoma · doi:10.1155/2011/837474 · Cited by 139
“FUS deficiency in mice resulted in defective B-lymphocyte development and activation, high levels of chromosomal instability, and perinatal death [74].”
BackgroundRegulation of Neuronal Excitability through Pumilio-Dependent Control of a Sodium Channel Gene
Mee, C., Pym, E. C. G., Moffat, K. G., & Baines, R. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2282-04.2004 · Cited by 143
Zebrafish as a model organism for neurodegenerative disease
Chia, K., Klingseisen, A., Sieger, D., & Priller, J. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.940484 · Cited by 138
“The absence of a phenotype typical for ALS upon FUS deletion in zebrafish is in line with previous findings in FUS knockout mouse models that displayed a range of phenotypes atypical of ALS (Hicks et al., 2000; Kino et al., 2015).”
ResultMutations in FUS cause FALS and SALS in French and French Canadian populations
Belzil, V., Valdmanis, P. N., Dion, P. A., Daoud, H., Kabashi, E., Noreau, A., Gauthier, J., Hince, P., Desjarlais, A., Bouchard, J. P., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181bbfeef · Cited by 133
The Splicing Factor U1C Represses EWS/FLI-mediated Transactivation
Knoop, L. L., & Baker, S. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001661200 · Cited by 133
Tan, A. Y., Riley, T., Coady, T. H., Bussemaker, H. J., & Manley, J. L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1203028109 · Cited by 136
“TLS and EWS were previously shown to be involved in pairing autosomal and sex chromosomes, respectively, during meiosis (24, 25).”
BackgroundFunctions of FUS/TLS From DNA Repair to Stress Response: Implications for ALS
Sama, R. R. K., Ward, C. L., & Bosco, D. A. (2014) · ASN NEURO · doi:10.1177/1759091414544472 · Cited by 134
Fus gene mutations in familial and sporadic amyotrophic lateral sclerosis
Rademakers, R., Stewart, H. G., DeJesus‐Hernandez, M., Krieger, C., Graff‐Radford, N. R., Fabros, M., Briemberg, H., Cashman, N. R., Eisen, A., & Mackenzie, I. R. (2010) · Muscle & Nerve · doi:10.1002/mus.21665 · Cited by 126
“FUS knockout mice show perinatal mortality.(26) The finding that FUS mutations cause FALS was the first association between this protein and a neurodegenerative condition.”
BackgroundAn ALS-associated mutation in the FUS 3′-UTR disrupts a microRNA–FUS regulatory circuitry
Modigliani, S. D., Morlando, M., Errichelli, L., Sabatelli, M., & Bozzoni, I. (2014) · Nature Communications · doi:10.1038/ncomms5335 · Cited by 127
Recent advances in the genetics of amyotrophic lateral sclerosis
Valdmanis, P. N., Daoud, H., Dion, P. A., & Rouleau, G. A. (2009) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-009-0030-9 · Cited by 121
Kino, Y., Washizu, C., Kurosawa, M., Yamada, M., Miyazaki, H., Akagi, T., Hashikawa, T., Doi, H., Takumi, T., Hicks, G. G., et al. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0202-6 · Cited by 132
“In this TLS strain, truncated FUS/TLS protein has been detected at very low levels in embryonic B cells [12].”
BackgroundResultInfluentialSelf-citationMouse models of ALS: Past, present and future
Lutz, C. M. (2018) · Brain Research · doi:10.1016/j.brainres.2018.03.024 · Cited by 129
Biomolecular condensates in neurodegeneration and cancer
Spannl, S., Tereshchenko, M., Mastromarco, G. J., Ihn, S. J., & Lee, H. O. (2019) · Traffic · doi:10.1111/tra.12704 · Cited by 116
Rhoads, S. N., Monahan, Z. T., Yee, D. S., & Shewmaker, F. P. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030886 · Cited by 113
Multifunctional zinc finger proteins in development and disease
Ladomery, M., & Dellaire, G. (2002) · Annals of Human Genetics · doi:10.1046/j.1469-1809.2002.00121.x · Cited by 115
Identification and characterization of FUS/TLS as a new target of ATM
Gardiner, M., Toth, R., Vandermoere, F., Morrice, N. A., & Rouse, J. (2008) · Biochemical Journal · doi:10.1042/bj20081135 · Cited by 111
PUM2, a novel murine puf protein, and its consensus RNA-binding site.
White, E. K., Moore-Jarrett, T., & Ruley, H. E. (2001) · Europe PMC (PubMed Central) · Cited by 111
Self-citationScaramuzzino, C., Monaghan, J., Milioto, C., Lanson, N. A., Maltare, A., Aggarwal, T., Casci, I., Fackelmayer, F. O., Pennuto, M., & Pandey, U. B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061576 · Cited by 108
“Knock down of FUS leads to genomic instability in mice [50,51].”
BackgroundMeißner, M., Lopato, S., Gotzmann, J., Sauermann, G., & Barta, A. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(02)00046-0 · Cited by 109
Stress granules at the intersection of autophagy and ALS
Monahan, Z. T., Shewmaker, F. P., & Pandey, U. B. (2016) · Brain Research · doi:10.1016/j.brainres.2016.05.022 · Cited by 110
“…functions ascribed to both FUS and TDP-43 (Avendano-Vazquez et al., 2012; Budini and Buratti, 2011; D'Alton et al., 2015; Dormann and Haass, 2011; Hicks et al., 2000; Lagier-Tourenne et al., 2010; Mastrocola et al., 2013; Patel et al., 2015a; Rulten et al., 2014; Sama et al., 2014; Wang et al.,…”
BackgroundInfluentialRole of FET proteins in neurodegenerative disorders
Svetoni, F., Frisone, P., & Paronetto, M. P. (2016) · RNA Biology · doi:10.1080/15476286.2016.1211225 · Cited by 110
“but the molecular mechanisms affected by EWS and FUS deficiencies are different.(27,28) Mating of Fus/Tls¡/¡ animals with wild-type counterparts revealed complete male sterility and reduced fertility of females.”
BackgroundBelly, A., Moreau-Gachelin, F., Sadoul, R., & Goldberg, Y. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2004.12.071 · Cited by 107
Axonal transport defects are a common phenotype in Drosophila models of ALS
Baldwin, K. R., Godena, V. K., Hewitt, V. L., & Whitworth, A. J. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw105 · Cited by 111
Expression of human FUS protein in Drosophila leads to progressive neurodegeneration
Chen, Y., Yang, M., Deng, J., Chen, X., Ye, Y., Zhu, L., Liu, J., Ye, H., Shen, Y., Li, Y., et al. (2011) · Protein & Cell · doi:10.1007/s13238-011-1065-7 · Cited by 103
“FUS-deficient mice show defects in B cell development, chromosomal instability and perinatal lethality (Hicks et al., 2000).”
BackgroundHumphrey, J., Birsa, N., Milioto, C., McLaughlin, M., Ule, A. M., Robaldo, D., Eberle, A. B., Kräuchi, R., Bentham, M. P., Brown, A., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa410 · Cited by 107
“The FUS KO construct used by the Bozzoni lab is a GeneTrap inserted into intron 12 (17), which leads to a partial FUS knockout (Supplementary Figure S1B).”
MethodBiomolecular condensates at sites of DNA damage: More than just a phase
Spegg, V., & Altmeyer, M. (2021) · DNA repair · doi:10.1016/j.dnarep.2021.103179 · Cited by 101
Importance of Functional Loss of FUS in FTLD/ALS
Ishigaki, S., & Sobue, G. (2018) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2018.00044 · Cited by 97
“Whole-body knockout of FUS in highly homogenous inbred C57B6 strain mice resulted in early neonatal death due to immune system defects (Hicks et al., 2000), whereas FUS KO in outbred mice had no developmental impairments (Kuroda et al., 2000).”
BackgroundLepourcelet, M., Tou, L., Cai, L., Sawada, J.-I., Lazar, A. J., Glickman, J. N., Williamson, J. A., Everett, A. D., Redston, M. S., Fox, E. A., et al. (2004) · Development · doi:10.1242/dev.01579 · Cited by 91
“Besides having a role in preserving genomic integrity (Baechtold et al., 1999; Hicks et al., 2000; Kuroda et al., 2000), TLS/Fus binds pre- and processed mRNAs, and engages in nucleocytoplasmic RNA transport (Iko et al., 2004; Lerga et al., 2001; Zinszner et al., 1997).”
BackgroundLi, S., Kuhne, W., Kulharya, A. S., Hudson, F. Z., Ha, K., Cao, Z., & Dynan, W. S. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp741 · Cited by 89
“In the other, deficiency resulted in defective B-cell development, spontaneous chromosomal instability and perinatal death (37).”
BackgroundEwing Sarcoma Protein: A Key Player in Human Cancer
Paronetto, M. P. (2013) · International Journal of Cell Biology · doi:10.1155/2013/642853 · Cited by 91
“Interestingly, Fus/Tlsnullmice showed a quite similar phenotype [24, 25]; however, while FUS/TLS is required for pairing of the autosomes, EWS appears to be involved in pairing the XY sex chromosomes during meiosis [23].”
BackgroundTLS Inhibits RNA Polymerase III Transcription
Tan, A. Y., & Manley, J. L. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00884-09 · Cited by 87
“TLS can promote D-loop formation, which is a step in the homologous recombination pathway for DNA repair (2, 7), and mice lacking TLS have high genomic instability and enhanced sensitivity to radiation (25, 38).”
BackgroundLing, S., Dastidar, S. G., Tokunaga, S., Ho, W. Y., Lim, K., Ilieva, H. S., Parone, P. A., Tyan, S.-H., Tse, T. M., Chang, J., et al. (2019) · eLife · doi:10.7554/elife.40811 · Cited by 87
“To rule out this possibility, we produced FUS mice (in a pure C57BL/6 background) in which both endogenous FUS alleles were disrupted (Hicks et al., 2000) (Figure 8A).”
BackgroundThe neurobiology of amyotrophic lateral sclerosis
Bento‐Abreu, A., Damme, P. V., Bosch, L. V. D., & Robberecht, W. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07260.x · Cited by 89
“FUS ⁄ TLS-knockout mice die immediately after birth (Hicks et al., 2000) or are rarely alive at weaning (Kuroda et al., 2000).”
Background
Metadata
- Authors
- Hicks, G. G., Singh, N., Nashabi, A., Mai, S., Bozek, G., Klewes, L., Arapovic, D., White, E. K., Koury, M. J., Oltz, E. M., Van Kaer, L., & Ruley, H. E.
- Affiliations
- University of Manitoba (CA)
- Howard Hughes Medical Institute (US)
- Vanderbilt University (US)
- Corresponding author
- Hicks, Geoffrey G.
- Venue
- Nature Genetics
- Published
- 2000-02
- Volume
- 24
- Issue
- 2
- Pages
- 175-179
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2080964315
- Cited by
- 299
- References
- 31
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 10 · 2022: 17 · 2021: 19 · 2020: 10 · 2019: 17 · 2018: 21 · 2017: 10 · 2016: 26 · 2015: 12 · 2014: 18 · 2013: 23 · 2012: 13
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01hg000684-04a1)
- National Human Genome Research Institute (R01HG00684)
- National Cancer Institute (P30CA042014)
- National Center for Research Resources (R01RR013166)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- FUS gene, TLS, B cell development, B cell activation, chromosomal instability, genome stability, perinatal lethality, nuclear ribonucleoprotein, transcription factors
- MeSH terms
- Animals, Animals, Newborn, B-Lymphocytes, Bone Marrow Cells, Chimera, Crosses, Genetic, Female, Genotype, Humans, Liver, Lymphocyte Activation, Male, Mice, Inbred C57BL, Ribonucleoproteins, Spleen, Restriction Mapping, RNA-Binding Proteins, Mice, Knockout, Heterogeneous-Nuclear Ribonucleoproteins, RNA-Binding Protein FUS, Mice
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