Functional Inactivation of the Genome-Wide Association Study Obesity Gene Neuronal Growth Regulator 1 in Mice Causes a Body Mass Phenotype
Open accessAbstract
To date, genome-wide association studies (GWAS) have identified at least 32 novel loci for obesity and body mass-related traits. However, the causal genetic variant and molecular mechanisms of specific susceptibility genes in relation to obesity are yet to be fully confirmed and characterised. Here, we examined whether the candidate gene NEGR1 encoding the neuronal growth regulator 1, also termed neurotractin or Kilon, accounts for the obesity association. To characterise the function of NEGR1 for body weight control in vivo, we generated two novel mutant mouse lines, including a constitutive NEGR1-deficient mouse line as well as an ENU-mutagenised line carrying a loss-of-function mutation (Negr1-I87N) and performed metabolic phenotypic analyses. Ablation of NEGR1 results in a small but steady reduction of body mass in both mutant lines, accompanied with a small reduction in body length in the Negr1-I87N mutants. Magnetic resonance scanning reveals that the reduction of body mass in Negr1-I87N mice is due to a reduced proportion of lean mass. Negr1-I87N mutants display reduced food intake and physical activity while normalised energy expenditure remains unchanged. Expression analyses confirmed the brain-specific distribution of NEGR1 including strong expression in the hypothalamus. In vitro assays show that NEGR1 promotes cell-cell adhesion and neurite growth of hypothalamic neurons. Our results indicate a role of NEGR1 in the control of body weight and food intake. This study provides evidence that supports the link of the GWAS candidate gene NEGR1 with body weight control.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There is a genetic correlation between ASD and social communication difficulties at age 8 in a non-ASD population sample (rG=0.375, p=0.0028).
“we confirm the genetic correlation with social communication difficulties at age 8 in a non-ASD population sample reported previously based on a subset of the ASD sample 70 ( 𝑟 𝐺 = 0.375, p = 0.0028).”
From Identification of common genetic risk variants for autism spectrum disorder (2019) · cites this paper as [70]
The Materials and Methods passages on time-course analysis concern genotype effects in mice, not ASD or social communication in children (page unavailable). Searches for the age-8 social-communication finding, ASD, and the reported correlation and p-value found no passage addressing the claim. (LLM, conf=0.78)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mixed-Effects Models in S and S-PLUS
(2001) · Technometrics · doi:10.1198/tech.2001.s574 · Cited by 9,278 · see citing works
Genetics of Food Intake Self-Regulation in Childhood: Literature Review and Research Opportunities
Faith, M. S., Carnell, S., & Kral, T. V. E. (2013) · Human Heredity · doi:10.1159/000353879 · Cited by 7,628 · see citing works
Everitt, B. S. (2001) · Psychology Press eBooks · doi:10.4324/9781410605542-11 · Cited by 6,877 · see citing works
Central nervous system control of food intake
Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., & Baskin, D. G. (2000) · Nature · doi:10.1038/35007534 · Cited by 6,451 · see citing works
Diggle, P. J., Heagerty, P. J., Liang, K., & Zeger, S. L. (2002) · doi:10.1093/oso/9780198524847.001.0001 · Cited by 3,388 · see citing works
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
MAGIC, Speliotes, E. K., on behalf of Procardis Consortium, Willer, C. J., Berndt, S. I., Monda, K. L., Thorleifsson, G., Jackson, A. U., Allen, H. L., Lindgren, C. M., et al. (2010) · Nature Genetics · doi:10.1038/ng.686 · Cited by 2,912 · see citing works
the GIANT Consortium (2009) · Nature Genetics · doi:10.1038/ng.287 · Cited by 1,720 · see citing works
Thorleifsson, G., Walters, G. B., Gudbjartsson, D. F., Steinthorsdottir, V., Sulem, P., Helgadottir, A., Styrkarsdottir, U., Gretarsdottir, S., Thorlacius, S., Jonsdottir, I., et al. (2009) · Nature Genetics · doi:10.1038/ng.274 · Cited by 1,375 · see citing works
Klaman, L. D., Boss, O., Peroni, O. D., Kim, J. K., Martino, J. L., Zabolotny, J. M., Moghal, N., Lubkin, M., Kim, Y.-B., Sharpe, A. H., et al. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.15.5479-5489.2000 · Cited by 1,235 · see citing works
Generation and Analysis of Interleukin-4 Deficient Mice
Kühn, R., Rajewsky, K., & Müller, W. (1991) · Science · doi:10.1126/science.1948049 · Cited by 1,229 · see citing works
Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons
Hahn, T. M., Breininger, J. F., Baskin, D. G., & Schwartz, M. W. (1998) · Nature Neuroscience · doi:10.1038/1082 · Cited by 1,164 · see citing works
Durocher, Y. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.2.e9 · Cited by 1,041 · see citing works
Introduction to Graphical Modelling
Edwards, D. (2000) · Springer texts in statistics · doi:10.1007/978-1-4612-0493-0 · Cited by 809 · see citing works
Neuroblastoma × spinal cord (NSC) hybrid cell lines resemble developing motor neurons
Cashman, N. R., Durham, H. D., Blusztajn, J. K., Oda, K., Tabira, T., Shaw, I. T., Dahrouge, S., & Antel, J. P. (1992) · Developmental Dynamics · doi:10.1002/aja.1001940306 · Cited by 724 · see citing works
She, P., Reid, T., Bronson, S. K., Vary, T. C., Hajnal, A. S., Lynch, C. J., & Hutson, S. M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.08.003 · Cited by 360 · see citing works
A Mouse Model for the Metabolic Effects of the Human Fat Mass and Obesity Associated FTO Gene
Church, C., Lee, S., Bagg, E. A. L., McTaggart, J. S., Deacon, R. M. J., Gerken, T., Lee, A., Moir, L., Mecinović, J., Quwailid, M. M., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000599 · Cited by 325 · see citing works
Self-citationHeinrich, C., Nitta, N., Flubacher, A., Müller, M., Fahrner, A., Kirsch, M., Freiman, T. M., Suzuki, F., Depaulis, A., Frotscher, M., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5516-05.2006 · Cited by 303 · see citing works
Self-citationRenström, F., Payne, F., Nordström, A., Brito, E. C., Rolandsson, O., Hallmans, G., Barroso, I., Nordström, P., & Franks, P. W. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp041 · Cited by 225 · see citing works
Rougon, G., & Hobert, O. (2003) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.26.041002.131014 · Cited by 215 · see citing works
Bauer, F., Elbers, C. C., Adan, R. A. H., Loos, R. J. F., Onland‐Moret, N. C., Grobbee, D. E., van Vliet‐Ostaptchouk, J. V., Wijmenga, C., & van der Schouw, Y. T. (2009) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.27781 · Cited by 201 · see citing works
Introduction to Graphical Modelling
Edwards, D. (1995) · Springer texts in statistics · doi:10.1007/978-1-4684-0481-4 · Cited by 195 · see citing works
Zhao, J., Bradfield, J. P., Li, M., Wang, K., Zhang, H., Kim, C., Annaiah, K., Glessner, J., Thomas, K., Garris, M., et al. (2009) · Obesity · doi:10.1038/oby.2009.159 · Cited by 189 · see citing works
Elks, C. E., Loos, R. J. F., Sharp, S. J., Langenberg, C., Ring, S. M., Timpson, N. J., Ness, A., Smith, G. D., Dunger, D. B., Wareham, N. J., et al. (2010) · PLoS Medicine · doi:10.1371/journal.pmed.1000284 · Cited by 182 · see citing works
Sellar, G. C., Watt, K. P., Rabiasz, G. J., Stronach, E. A., Li, L., Miller, E. P., Massie, C. E., Miller, J. C., Contreras‐Moreira, B., Scott, D., et al. (2003) · Nature Genetics · doi:10.1038/ng1183 · Cited by 179 · see citing works
A gene-driven ENU-based approach to generating an allelic series in any gene
Quwailid, M. M., Hugill, A. J., Dear, N. T., Vizor, L., Wells, S. E., Horner, E., Fuller, S., Weedon, J., McMath, H., Woodman, P., et al. (2004) · Mammalian Genome · doi:10.1007/s00335-004-2379-z · Cited by 144 · see citing works
Self-citationHotta, K., Nakamura, M., Nakamura, T., Matsuo, T., Nakata, Y., Kamohara, S., Miyatake, N., Kotani, K., Komatsu, R., Itoh, N., et al. (2009) · Journal of Human Genetics · doi:10.1038/jhg.2009.106 · Cited by 135 · see citing works
Ng, M. C. Y., Tam, C. H. T., So, W. Y., Ho, J. S. K., Chan, A. W. H., Lee, H. M., Wang, Y., Lam, V. K. L., Chan, J. C. N., & Ronald, C. W. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2077 · Cited by 133 · see citing works
Angelis, E. D. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.1.1 · Cited by 126 · see citing works
Funatsu, N., Miyata, S., Kumanogoh, H., Shigeta, M., Hamada, K., Endo, Y., Sokawa, Y., & Maékawa, S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.12.8224 · Cited by 119 · see citing works
Chen, J., Lui, W., Vos, M. D., Clark, G. J., Takahashi, M., Schoumans, J., Khoo, S. K., Petillo, D., Lavery, T. T., Sugimura, J., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00269-1 · Cited by 112 · see citing works
Gil, O. D., Zanazzi, G., Struyk, A. F., & Salzer, J. L. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-22-09312.1998 · Cited by 111 · see citing works
Cui, Y., Ying, Y., van Hasselt, A., Ng, K. M., Yu, J. Q., Zhang, Q., Jin, J., Liu, D., Rhim, J. S., Rha, S. Y., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002990 · Cited by 105 · see citing works
Schäfer, M., Bräuer, A. U., Savaskan, N. E., Rathjen, F. G., & Brümmendorf, T. (2005) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.04.010 · Cited by 86 · see citing works
Self-citationIgLON cell adhesion molecule Kilon is a crucial modulator for synapse number in hippocampal neurons
Hashimoto, T., Yamada, M., Maekawa, S., Nakashima, T., & Miyata, S. (2008) · Brain Research · doi:10.1016/j.brainres.2008.05.069 · Cited by 71 · see citing works
Novel phenotypes identified by plasma biochemical screening in the mouse
Hough, T., Nolan, P. M., Tsipouri, V., Toye, A. A., Gray, I. C., Goldsworthy, M. E., Moir, L., Cox, R., Clements, S., Glenister, P. H., et al. (2002) · Mammalian Genome · doi:10.1007/s00335-002-2188-1 · Cited by 69 · see citing works
Self-citationMarg, A., Sirim, P., Spaltmann, F., Plagge, A., Kauselmann, G., Buck, F., Rathjen, F. G., & Brümmendorf, T. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.4.865 · Cited by 69 · see citing works
Self-citationMiyata, S., Matsumoto, N., Taguchi, K., Akagi, A., Iino, T., Funatsu, N., & Maekawa, S. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00873-4 · Cited by 66 · see citing works
Implication of European-derived adiposity loci in African Americans
Hester, J. M., Wing, M. R., Li, J., Palmer, N., Xu, J., Hicks, P. J., Roh, B. H., Norris, J., Wagenknecht, L., Langefeld, C., et al. (2011) · International Journal of Obesity · doi:10.1038/ijo.2011.131 · Cited by 62 · see citing works
Lee, K., Byun, M.-J., Kang, K.-S., Park, E.-W., Lee, S. H., Cho, S., Kim, H.-Y., Kim, K.-W., Lee, T., Park, J., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016356 · Cited by 62 · see citing works
Genes and lifestyle factors in obesity: results from 12 462 subjects from MONICA/KORA
Holzapfel, C., Grallert, H., Huth, C., Wahl, S., Fischer, B., Döring, A., Rückert, I., Hinney, A., Hebebrand, J., Wichmann, H. ‐., et al. (2010) · International Journal of Obesity · doi:10.1038/ijo.2010.79 · Cited by 62 · see citing works
Kilpeläinen, T. O., den Hoed, M., Ong, K. K., Grøntved, A., Brage, S., Jameson, K. E., Cooper, C. C., Khaw, K., Ekelund, U., Wareham, N. J., et al. (2011) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.000828 · Cited by 61 · see citing works
Gil, O. D., Zhang, L., Chen, S., Ren, Y. Q., Pimenta, A., Zanazzi, G., Hillman, D., Levitt, P., & Salzer, J. L. (2002) · Journal of Neurobiology · doi:10.1002/neu.10050 · Cited by 61 · see citing works
Reed, J. E., Dunn, J. R., Du Plessis, D. G., Shaw, E. J., Reeves, P., Gee, A. L., Warnke, P. C., Sellar, G. C., Moss, D. J., & Walker, C. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2006.00786.x · Cited by 61 · see citing works
Genetic Deletion of Lsamp Causes Exaggerated Behavioral Activation in Novel Environments
Catania, E. H., Pimenta, A. F., & Levitt, P. R. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.11.022 · Cited by 59 · see citing works
The IgLON Family in Epithelial Ovarian Cancer: Expression Profiles and Clinicopathologic Correlates
Ntougkos, E., Rush, R., Scott, D., Frankenberg, T., Gabra, H., Smyth, J. F., & Sellar, G. C. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-2388 · Cited by 57 · see citing works
Schaefer, M. K. E., Schmalbruch, H., Buhler, E., Lopez, C., Martín-Martín, N., Guénet, J., & Haase, G. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1599-07.2007 · Cited by 56 · see citing works
Qiu, S., Champagne, D. L., Peters, M. M., Catania, E. H., Weeber, E. J., Levitt, P. R., & Pimenta, A. F. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.02.013 · Cited by 52 · see citing works
Walley, A. J., Jacobson, P., Falchi, M., Bottolo, L., Andersson‐Assarsson, J. C., Petretto, E. G., Bonnefond, A., Vaillant, E., Lecœur, C., Vatin, V., et al. (2011) · International Journal of Obesity · doi:10.1038/ijo.2011.22 · Cited by 51 · see citing works
Lodge, A. P., Howard, M. R., McNamee, C. J., & Moss, D. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00184-4 · Cited by 48 · see citing works
L1 syndrome mutations impair neuronal L1 function at different levels by divergent mechanisms
Schäfer, M. K. E., Nam, Y.-C., Moumen, A., Keglowich, L., Bouché, E., Küffner, M., Bock, H. H., Rathjen, F. G., Raoul, C., & Frotscher, M. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.05.029 · Cited by 40 · see citing works
Self-citationLower anxiety and a decrease in agonistic behaviour in Lsamp-deficient mice
Innos, J., Philips, M., Leidmaa, E., Heinla, I., Raud, S., Reemann, P., Plaas, M., Nurk, K., Kurrikoff, K., Matto, V., et al. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.09.019 · Cited by 39 · see citing works
Pimenta, A. F., & Levitt, P. R. (2004) · Genomics · doi:10.1016/j.ygeno.2003.11.013 · Cited by 29 · see citing works
Lodge, A. P., McNamee, C. J., Howard, M. R., Reed, J. E., & Moss, D. (2001) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2001.0964 · Cited by 24 · see citing works
Akeel, M., McNamee, C. J., Youssef, S. S., & Moss, D. (2010) · Brain Research · doi:10.1016/j.brainres.2010.12.028 · Cited by 23 · see citing works
Marx, M., Diestel, S., Bozon, M., Keglowich, L., Drouot, N., Bouché, E., Frébourg, T., Minz, M., Saugier-Véber, P., Castellani, V., et al. (2012) · Neurogenetics · doi:10.1007/s10048-011-0307-4 · Cited by 14 · see citing works
Self-citationSugimoto, C., Maékawa, S., & Miyata, S. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06513.x · Cited by 11 · see citing works
Guijarro, C., Rutz, S., Rothmaier, K., Turiault, M., Zhi, Q., Naumann, T., Frotscher, M., Tronche, F., Jackisch, R., & Kretz, O. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03728.x · Cited by 11 · see citing works
Self-citation
Flagged first, then by citations
2 of the 59 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- [40]Lauritzen SL (2004) Graphical Models;. Atkinson AC, Copas JB, Pierce DA, Schervish MJ, Titterington DM, editors. Oxford University Press.
- [46]Rougon G, Hobert O (2003) New Insights into the Diversity and Function of Neuronal Immunoglobulin Superfamily Molecules. Annual Review of Neuroscience 26: 207– 238. 12598678
- [48]Renström F, Payne F, Nordström A, Brito EC, Rolandsson O, et al (2009) Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden. Hum Mol Genet 18: 1489– 1496. 19164386 PMC2664142
- [58]Lauritzen S, Atkinson A, Copas J, Pierce D, Schervish M, et al (2004) Graphical Models. Oxford University Press.
Cited by
Sorted by citations
Genetic studies of body mass index yield new insights for obesity biology
Study, T. L. C., Locke, A. E., The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The, G. L. G. C., The, I. C. B. P., The MAGIC Investigators, The MuTHER Consortium, et al. (2015) · Nature · doi:10.1038/nature14177 · Cited by 4,534 · see citing works
eQTLGen, Wray, N. R., 23andMe, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., Adams, M. J., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0090-3 · Cited by 3,005 · see citing works
Identification of common genetic risk variants for autism spectrum disorder
Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium, Grove, J., BUPGEN, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 23andMe Research Team, Ripke, S., Als, T. D., Mattheisen, M., Walters, R. K., Won, H., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0344-8 · Cited by 2,421 · see citing works
The genetics of obesity: From discovery to biology
Loos, R. J. F., & Yeo, G. S. H. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-021-00414-z · Cited by 1,291 · see citing works
Depression and obesity: evidence of shared biological mechanisms
Milaneschi, Y., Simmons, W. K., van Rossum, E. F. C., & Penninx, B. W. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0017-5 · Cited by 1,073 · see citing works
Obesity genetics in mouse and human: back and forth, and back again
Yazdi, F., Clee, S. M., & Meyre, D. (2015) · PeerJ · doi:10.7717/peerj.856 · Cited by 197 · see citing works
Prebiotic and Probiotic Modulation of the Microbiota–Gut–Brain Axis in Depression
Radford‐Smith, D. E., & Anthony, D. C. (2023) · Nutrients · doi:10.3390/nu15081880 · Cited by 108 · see citing works
GWAS for BMI: a treasure trove of fundamental insights into the genetic basis of obesity
Speakman, J. R., Loos, R. J. F., O’Rahilly, S., Hirschhorn, J. N., & Allison, D. B. (2018) · International Journal of Obesity · doi:10.1038/s41366-018-0147-5 · Cited by 91 · see citing works
Common risk variants identified in autism spectrum disorder
Grove, J., Ripke, S., Als, T. D., Mattheisen, M., Walters, R., Won, H., Pallesen, J., Agerbo, E., Andreassen, O. A., Anney, R., et al. (2017) · doi:10.1101/224774 · Cited by 89 · see citing works
Negr1 controls adult hippocampal neurogenesis and affective behaviors
Noh, K., Lee, H., Choi, T.-Y., Joo, Y., Kim, S.-J., Kim, H., Kim, J. Y., Jahng, J. W., Lee, S., Choi, S.-Y., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0347-3 · Cited by 86 · see citing works
Szczurkowska, J., Pischedda, F., Pinto, B., Managò, F., Haas, C. A., Summa, M., Bertorelli, R., Papaleo, F., Schäfer, M. K. E., Piccoli, G., et al. (2018) · Brain · doi:10.1093/brain/awy190 · Cited by 75 · see citing works
Self-citationRukh, G., Sonestedt, E., Melander, O., Hedblad, B., Wirfält, E., Ericson, U., & Orho‐Melander, M. (2013) · Genes & Nutrition · doi:10.1007/s12263-013-0352-8 · Cited by 67 · see citing works
Genetics and epigenetics in the obesity phenotyping scenario
Trang, B. K., & Grant, S. F. A. (2023) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09804-6 · Cited by 66 · see citing works
Singh, K., Jayaram, M., Kaare, M., Leidmaa, E., Jagomäe, T., Heinla, I., Hickey, M. A., Kaasik, A., Schäfer, M. K., Innos, J., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-41991-8 · Cited by 65 · see citing works
Self-citationSingh, K., Loreth, D., Pöttker, B., Hefti, K., Innos, J., Schwald, K., Hengstler, H., Menzel, L., Sommer, C., Radyushkin, K., et al. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00030 · Cited by 65 · see citing works
Self-citationPritchard, V. L., Mäkinen, H., Vähä, J., Erkinaro, J., Orell, P., & Primmer, C. R. (2018) · Molecular Ecology · doi:10.1111/mec.14705 · Cited by 64 · see citing works
Speakman, J. R. (2013) · Human Heredity · doi:10.1159/000353585 · Cited by 61 · see citing works
The obesity-associated gene Negr1 regulates aspects of energy balance in rat hypothalamic areas
Boender, A. J., van Gestel, M. A., Garner, K. M., Luijendijk, M. C. M., & Adan, R. A. H. (2014) · Physiological Reports · doi:10.14814/phy2.12083 · Cited by 51 · see citing works
Approach to assessing determinants of glucose homeostasis in the conscious mouse
Hughey, C. C., Wasserman, D. H., Lee, R. S., & Lantier, L. (2014) · Mammalian Genome · doi:10.1007/s00335-014-9533-z · Cited by 50 · see citing works
Adult rat myelin enhances axonal outgrowth from neural stem cells
Poplawski, G. H. D., Lie, R., Hunt, M. A., Kumamaru, H., Kawaguchi, R., Lu, P., Schäfer, M. K. E., Woodruff, G., Robinson, J., Canete, P., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aal2563 · Cited by 49 · see citing works
Self-citationNeuronal growth regulator 1-deficient mice show increased adiposity and decreased muscle mass
Joo, Y., Kim, H., Lee, S.-J., & Lee, S. (2019) · International Journal of Obesity · doi:10.1038/s41366-019-0376-2 · Cited by 49 · see citing works
Mägi, R., Manning, S., Yousseif, A., Pucci, A. B. F., Santini, F., Karra, E., Querci, G., Pelosini, C., McCarthy, M. I., Lindgren, C. M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070735 · Cited by 48 · see citing works
Promoter-Specific Expression and Genomic Structure of IgLON Family Genes in Mouse
Vanaveski, T., Singh, K., Narvik, J., Eskla, K., Visnapuu, T., Heinla, I., Jayaram, M., Innos, J., Lilleväli, K., Philips, M., et al. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00038 · Cited by 44 · see citing works
Obesity gene NEGR1 associated with white matter integrity in healthy young adults
Dennis, E. L., Jahanshad, N., Braskie, M. N., Warstadt, N. M., Hibar, D. P., Omid Kohannim, A., Nir, T. M., McMahon, K. L., de Zubicaray, G. I., Montgomery, G. W., et al. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.07.041 · Cited by 39 · see citing works
Age and diet shape the genetic architecture of body weight in diversity outbred mice
Wright, K. M., Deighan, A. G., Francesco, A. D., Freund, A., Jojic, V., Churchill, G. A., & Raj, A. (2022) · eLife · doi:10.7554/elife.64329 · Cited by 37 · see citing works
Schlauch, K. A., Read, R. W., Lombardi, V. C., Elhanan, G., Metcalf, W. J., Slonim, A. D., & Grzymski, J. J. (2019) · G3 Genes Genomes Genetics · doi:10.1534/g3.119.400910 · Cited by 35 · see citing works
Impact of NEGR1 genetic variability on psychological traits of patients with eating disorders
Gamero‐Villarroel, C., González, L. M., Gordillo, I., Carrillo, J. A., Garcia-Herraiz, A., Flores, I., Rodríguez‐López, R., & Gervasini, G. (2014) · The Pharmacogenomics Journal · doi:10.1038/tpj.2014.53 · Cited by 34 · see citing works
Drabsch, T., Gatzemeier, J., Pfadenhauer, L. M., Hauner, H., & Holzapfel, C. (2018) · Advances in Nutrition · doi:10.1093/advances/nmy024 · Cited by 31 · see citing works
The Role of IgLON Cell Adhesion Molecules in Neurodegenerative Diseases
Salluzzo, M., Vianello, C., Abdullatef, S., Rimondini, R., Piccoli, G., & Carboni, L. (2023) · Genes · doi:10.3390/genes14101886 · Cited by 29 · see citing works
Feed Your Head: Neurodevelopmental Control of Feeding and Metabolism
Lee, D. A., & Blackshaw, S. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170347 · Cited by 29 · see citing works
Depression-Associated Gene Negr1-Fgfr2 Pathway Is Altered by Antidepressant Treatment
Carboni, L., Pischedda, F., Piccoli, G., Lauria, M., Musazzi, L., Popoli, M., Mathé, A. A., & Domenici, E. (2020) · Cells · doi:10.3390/cells9081818 · Cited by 29 · see citing works
Venkannagari, H., Kasper, J. M., Misra, A., Rush, S. A., Fan, S., Lee, H., Sun, H., Seshadrinathan, S., Machius, M., Hommel, J. D., et al. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.07.014 · Cited by 27 · see citing works
Leyden, G. M., Shapland, C. Y., Smith, G. D., Sanderson, E. C. M., Greenwood, M. P., Murphy, D., & Richardson, T. G. (2022) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.12.013 · Cited by 27 · see citing works
A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder
Maekawa, M., Ohnishi, T., Toyoshima, M., Shimamoto‐Mitsuyama, C., Hamazaki, K., Balan, S., Wada, Y., Esaki, K., Takagai, S., Tsuchiya, K. J., et al. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa145 · Cited by 26 · see citing works
Sánchez, J., Picó, C., Ahrens, W., Foraita, R., Fraterman, A., Moreno, L. A., Russo, P., Siani, A., Palou, A., & Consortia, O. B. O. T. I. A. I. F. (2017) · International Journal of Obesity · doi:10.1038/ijo.2017.132 · Cited by 25 · see citing works
Noh, K., Park, J.-C., Han, J., & Lee, S. J. (2020) · Experimental Neurobiology · doi:10.5607/en.2020.29.1.1 · Cited by 24 · see citing works
Kaur, P., Tan, J. R., Karolina, D. S., Sepramaniam, S., Armugam, A., Wong, P. T.-H., & Jeyaseelan, K. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.12.012 · Cited by 24 · see citing works
Genomic insights into local adaptation and phenotypic diversity of Wenchang chickens
Gu, L., Wu, R., Zheng, X., Fu, A., Xing, Z.-Y., Chen, Y., He, Z.-C., Lu, L., Qi, Y.-T., Chen, A., et al. (2023) · Poultry Science · doi:10.1016/j.psj.2023.103376 · Cited by 23 · see citing works
Cox, D. M., Butler, M. G., & Genovese, A. (2015) · Journal of Pediatric Genetics · doi:10.1055/s-0035-1554977 · Cited by 23 · see citing works
Discussing the Putative Role of Obesity-Associated Genes in the Etiopathogenesis of Eating Disorders
Gervasini, G., & Gamero‐Villarroel, C. (2015) · Pharmacogenomics · doi:10.2217/pgs.15.77 · Cited by 22 · see citing works
Physiological and genomic insight into neuroendocrine regulation of puberty in gilts
Lents, C. A., Lindo, A. N., Hileman, S. M., & Nonneman, D. (2020) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2020.106446 · Cited by 22 · see citing works
Moleres, A., Martínez, J. A., & Martí, A. (2012) · Current Obesity Reports · doi:10.1007/s13679-012-0036-5 · Cited by 19 · see citing works
Zhang, Q., Liu, C., Li, Q., Li, J., Wu, Y., & Liu, J. (2019) · Biochimie · doi:10.1016/j.biochi.2019.07.020 · Cited by 18 · see citing works
Kaare, M., Mikheim, K., Lilleväli, K., Kilk, K., Jagomäe, T., Leidmaa, E., Piirsalu, M., Porosk, R., Singh, K., Reimets, R., et al. (2021) · Biomedicines · doi:10.3390/biomedicines9091148 · Cited by 18 · see citing works
Self-citationTilley, S. K., Joseph, R. M., Kuban, K., Dammann, O., O’Shea, T. M., & Fry, R. C. (2017) · PLoS ONE · doi:10.1371/journal.pone.0176953 · Cited by 17 · see citing works
Liu, L., Yi, J., Ray, W. K., Vu, L. T., Helm, R. F., Siegel, P. B., Cline, M. A., & Gilbert, E. R. (2019) · Nutrition and Diabetes · doi:10.1038/s41387-019-0081-1 · Cited by 13 · see citing works
Su, F., Pfundstein, G., Sah, S. K., Zhang, S., Keable, R., Hagan, D. W., Sharpe, L. J., Clemens, K. J., Begg, D. P., Phelps, E. A., et al. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16279 · Cited by 12 · see citing works
Kaare, M., Jayaram, M., Jagomäe, T., Singh, K., Kilk, K., Mikheim, K., Leevik, M., Leidmaa, E., Varul, J., Nõmm, H., et al. (2022) · Brain Sciences · doi:10.3390/brainsci12121696 · Cited by 12 · see citing works
Self-citationRana, S., & Bhatti, A. A. (2021) · Scientific Reports · doi:10.1038/s41598-021-87702-0 · Cited by 11 · see citing works
Kumar, P., & Mahalingam, K. (2018) · 3 Biotech · doi:10.1007/s13205-018-1463-0 · Cited by 10 · see citing works
Gene expression atlas of energy balance brain regions
Rosa, M. C. D., Glover, H. J., Stratigopoulos, G., LeDuc, C. A., Su, Q., Shen, Y., Sleeman, M. W., Chung, W. K., Leibel, R. L., Altarejos, J. Y., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.149137 · Cited by 9 · see citing works
Genetic Landscape of Obesity in Children: Research Advances and Prospects
Khusainova, R. I., Minniakhmetov, I. R., Vasyukova, O. V., Yalaev, B. I., Ринатович, С. Р., Kopytina, D. A., Guseinova, R. M., Dobreva, E. A., Mel'nichenko, G. A., Dedov, I. I., et al. (2025) · Journal of Obesity · doi:10.1155/jobe/9186826 · Cited by 8 · see citing works
Rödig, N., Sellmann, K., Guilherme, M. D. S., Nguyen, V. T. T., Cleppien, D., Stroh, A., May‐Simera, H., & Endres, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314506 · Cited by 8 · see citing works
Mazzaferro, E., Mújica, E., Zhang, H., Emmanouilidou, A., Jenseit, A., Evcimen, B., Metzendorf, C., Dethlefsen, O., Loos, R. J. F., Vienberg, S. G., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-89823-2 · Cited by 8 · see citing works
Pick, J. L., Hatakeyama, M., Ihle, K. E., Gasparini, J., Haussy, C., Ishishita, S., Matsuda, Y., Yoshimura, T., Kanaoka, M. M., Shimizu‐Inatsugi, R., et al. (2020) · Evolution Letters · doi:10.1002/evl3.166 · Cited by 8 · see citing works
Singh, K., Jayaram, M., Hanumantharaju, A., Tõnissoo, T., Jagomäe, T., Mikheim, K., Muthuraman, S., Gilbert, S. F., Plaas, M., Schäfer, M. K. E., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-73358-z · Cited by 7 · see citing works
Self-citationHoffmans, C. C. A., Jan Treur, A., & Hendrikse, S. C. F. (2024) · Studies in computational intelligence · doi:10.1007/978-3-031-76516-2_12 · Cited by 7 · see citing works
1p31.1 microdeletion including only NEGR1 gene in two patients
Tassano, E., Uccella, S., Giacomini, T., Fiorio, P., Tavella, E., Malacarne, M., Gimelli, G., Coviello, D. A., & Ronchetto, P. (2020) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2020.103919 · Cited by 7 · see citing works
Han, B., Yan, S., Xu, Q., Ni, J., Wei, X., Feng, G.-J., Zhang, H., Li, B., Zhang, L., & Pei, Y. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab911 · Cited by 7 · see citing works
Erdoğan, M. Ö., Avcı, K., Yıldız, S. H., Söylemez, E. S. A., Söylemez, Z., Varol, N., & Solak, M. (2018) · Biotechnology & Biotechnological Equipment · doi:10.1080/13102818.2018.1533430 · Cited by 6 · see citing works
Association of the NEGR1 rs2815752 with obesity and related traits in Pakistani females
Rana, S., & Mobin, M. (2020) · Upsala Journal of Medical Sciences · doi:10.1080/03009734.2020.1756996 · Cited by 6 · see citing works
Ninomiya, M., Matsuo, J., Sasayama, D., Hori, H., Teraishi, T., Ota, M., Hattori, K., Noda, T., Ishida, I., Shibata, S., et al. (2016) · Acta Neuropsychiatrica · doi:10.1017/neu.2016.66 · Cited by 6 · see citing works
Tan, R. P. A., Kozlova, I., Su, F., Sah, S. K., Keable, R., Hagan, D. W., Bustamante, S., Du, X., Osborne, B., Turner, N. A., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.02.08.479601 · Cited by 6 · see citing works
Li, Y., Li, J., Sun, T., He, Z., Liu, C., Li, Z., Wu, Y., & Xiang, H. (2025) · Lipids in Health and Disease · doi:10.1186/s12944-025-02437-5 · Cited by 5 · see citing works
Genetics of Depressive Disorders: Candidate Genes and Genome-Wide Association Studies
Rafikova, E., Рысков, А. П., & Vasilyev, V. A. (2020) · Russian Journal of Genetics · doi:10.1134/s1022795420080116 · Cited by 5 · see citing works
Knebel, B., Lehr, S., Janssen, O. E., Hahn, S., Jacob, S., Nitzgen, U., Müller‐Wieland, D., & Kotzka, J. (2016) · Molecular Biology Reports · doi:10.1007/s11033-016-4080-1 · Cited by 5 · see citing works
Habicher, J., Sanvido, I., Bühler, A., Sartori, S., Piccoli, G., & Carl, M. (2024) · Genes · doi:10.3390/genes15030363 · Cited by 4 · see citing works
Chalmers, J., Tung, Y. C. L., Ch, L., O’Kane, C. J., O’Rahilly, S., & Yeo, G. S. H. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101127 · Cited by 4 · see citing works
Negr1 Deficiency Modulates Sex-Specific Neurobehavioral Adaptations to Social Isolation
Reinsberg, A., Singh, K., Jayaram, M., Mikheim, K., Philips, M., & Vasar, E. (2025) · Brain Sciences · doi:10.3390/brainsci15121286 · Cited by 3 · see citing works
Agopiantz, M., Xandre-Rodriguez, L., Jin, B., Urbistondoy, G., Ialy‐Radio, C., Chalbi, M., Wolf, J., Ziyyat, A., & Lefèvre, B. (2016) · Reproduction Fertility and Development · doi:10.1071/rd15367 · Cited by 3 · see citing works
Hypólito, T. M. (2021) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.6.2021.tde-24062021-193148 · Cited by 3 · see citing works
Management of Obesity: Finding the Metabolic Magic Wand
Kalra, S., Kapoor, N., & Jacob, J. J. (2022) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.369156 · Cited by 3 · see citing works
Muthuraman, S., Jayaram, M., Promet, L., Jagomäe, T., Devarajan, A. K., Hade, A.-C., Philips, M., Singh, K., & Vasar, E. (2026) · Biology of Sex Differences · doi:10.1186/s13293-026-00890-0 · Cited by 2 · see citing works
Obesity and depression: A molecular and epidemiological view of two comorbid disorders
Cuenca-Ecuador., U. C. D. C., Guzmán, M. G. V., Garzón, M., & Ortíz, R. (2022) · Gaceta Médica de Caracas · doi:10.47307/gmc.2022.130.s3.25 · Cited by 2 · see citing works
Jia, H., & Liu, D. (2025) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-025-01975-3 · Cited by 1 · see citing works
Kuuskmäe, C., Mikheim, K., Mohammadrahimi, N., Kilk, K., Kaare, M., Jayaram, M., Ilnitski, G., Leidmaa, E., Philips, M., & Vasar, E. (2026) · Scientific Reports · doi:10.1038/s41598-026-35968-7 · Cited by 1 · see citing works
Pick, J. L., Hatakeyama, M., Ihle, K. E., Gasparini, J., Haussy, C., Ishishita, S., Matsuda, Y., Yoshim, T., Kanaoka, M. M., Shimizu‐Inatsugi, R., et al. (2020) · Evolution Letters · doi:10.1002/evl3.v4.3 · Cited by 1 · see citing works
Genetic Determinants of Habitual Physical Activity and Overweight and Obesity
Lee, H. (2013) · OpenCommons - UConn (University of Connecticut)
Hypothalamic Regulation of Food Intake in Obese and Anorexic Avian Models
Yi, J. (2016) · VTechWorks (Virginia Tech)
Dalman, M. R. (2014) · OhioLink ETD Center (Ohio Library and Information Network)
Nürnberger, J. I. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735152734.793563005
NEGR1 can influence symptom severity in fluoxetine treated major depression disorder patientsPreprint
Bayoğlu, B., Akdeniz, G., Kocabaşoğlu, N., Poyraz, C. A., Dırıcan, A., & Cengiz, M. (2024) · Research Square · doi:10.21203/rs.3.rs-4421084/v1
Celebioglu, H. B. O., Öztürk, A. P., Poyrazoğlu, Ş., & Tuncer, F. N. (2026) · Genes · doi:10.3390/genes17050530
Fang, Y., Sun, J., Yang, Y., Li, P., & Ni, W. (2026) · npj Systems Biology and Applications · doi:10.1038/s41540-026-00820-1
Cellular and molecular census of the pleiotropic disease locus Negr1 in zebrafishPreprint
González-Suarez, A., Pola-Morell, L., & López‐Schier, H. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.08.757516
Muthuraman, S., Jayaram, M., Lavõgina, D., Pilve, B., Reinsberg, A., Mikheim, K., Vasar, E., Philips, M., & Singh, K. (2026) · Scientific Reports · doi:10.1038/s41598-026-77023-5
Hanisch, J. J. (2013) · DigitalGeorgetown (Georgetown University Library)
- Authors
- Lee, A. W. S., Hengstler, H., Schwald, K., Berriel-Diaz, M., Loreth, D., Kirsch, M., Kretz, O., Haas, C. A., de Angelis, M. H., Herzig, S., Brümmendorf, T., Klingenspor, M., Rathjen, F. G., Rozman, J., Nicholson, G., Cox, R. D., & Schäfer, M. K. E.
- Affiliations
- Mary Lyon Centre at MRC Harwell (GB)
- University of Freiburg (DE)
- University Medical Center Freiburg (DE)
- German Cancer Research Center (DE)
- Max Delbrück Center (DE)
- Technical University of Munich (DE)
- Helmholtz Munich (DE)
- University of Oxford (GB)
- Corresponding author
- Lee, Angela W. S.
- Cox, Roger D.
- Schäfer, Michael K. E.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-07-23
- Volume
- 7
- Issue
- 7
- Pages
- e41537
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3402391
- OpenAlex
- W2098560069
- Cited by
- 84
- References
- 59
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 11 · 2019: 8 · 2018: 10 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 5 · 2013: 6 · 2012: 1
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
- mediaTUM (Technical University of Munich) (submittedVersion, cc-by)
- Site cant be reached (submittedVersion, cc-by)
- Funders
- Wellcome Trust (081219)
- Deutsche Forschungsgemeinschaft
- Albert-Ludwigs-Universität Freiburg
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- NEGR1, obesity, body mass, weight management, dietary intake, hypothalamus, hypothalamic neurons, neurite outgrowth, cell-cell adhesion, lean body mass, energy expenditure, loss-of-function mutations, obesity susceptibility genes
- MeSH terms
- Alleles, Animals, Body Height, Body Weight, Cell Adhesion, Cell Line, Eating, Endoplasmic Reticulum, Energy Metabolism, Female, Genotype, Humans, Hypothalamus, Male, Membrane Proteins, Motor Activity, Nerve Tissue Proteins, Obesity, Phenotype, Cell Adhesion Molecules, Neuronal, Neurites, Gene Silencing, Mice, Genome-Wide Association Study, Gene Knockout Techniques, Diet, High-Fat
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review