Hoxb8 Is Required for Normal Grooming Behavior in Mice
Open accessAbstract
Repertoires of grooming behaviors critical to survival are exhibited by most animal species, including humans. Genes that influence this complex behavior are unknown. We report that mice with disruptions of Hoxb8 show, with 100% penetrance, excessive grooming leading to hair removal and lesions. Additionally, these mice excessively groom normal cagemates. We have been unable to detect any skin or PNS abnormalities in Hoxb8 mutants. These observations suggest that the excessive, pathological grooming exhibited by these mice results from CNS abnormalities. Consistent with this interpretation, we demonstrate Hoxb8 expression in regions of the adult mouse CNS previously implicated in the control of grooming. The aberrant behavior observed in Hoxb8 mutants is not unlike that of humans suffering from the OC-spectrum disorder, trichotillomania. Interestingly, Hoxb8 is expressed in regions of the CNS known as the "OCD-circuit."
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Three animal models exhibit markedly elevated grooming: the HoxB8 knockout mouse, the SAPAP3 knockout mouse, and the SliTrk5 knockout mouse.
“Three models in particular exhibit markedly elevated grooming: the HoxB8 knockout mouse,[20] the SAPAP3 knockout mouse,[21] and the SliTrk5 knockout mouse.[22]”
From Trichotillomania (hair pulling disorder) (2019) · cites this paper as [20]
Cites
Toward a neurobiology of obsessive-compulsive disorder
Graybiel, A. M., & Rauch, S. L. (2000) · Neuron · doi:10.1016/s0896-6273(00)00113-6 · Cited by 864 · see citing works
Neuroimaging and frontal–subcortical circuitry in obsessive–compulsive disorder
Saxena, S., Brody, A. L., Schwartz, J. M., & Baxter, L. R. (1998) · British Journal of Psychiatry · doi:10.1192/s0007125000297870 · Cited by 831 · see citing works
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Microglia development and function
Nayak, D., Roth, T. L., & McGavern, D. B. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120240 · Cited by 1,154 · see citing works
Striatal Plasticity and Basal Ganglia Circuit Function
Kreitzer, A. C., & Malenka, R. C. (2008) · Neuron · doi:10.1016/j.neuron.2008.11.005 · Cited by 1,009 · see citing works
Kosik, K. S. (2006) · Nature reviews. Neuroscience · doi:10.1038/nrn2037 · Cited by 823 · see citing works
“Curiously, a behavioural syndrome that is characterized by excessive grooming leading to hair removal and lesions has also been attributed to Hoxb8 (Ref”
BackgroundCortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice
Welch, J. M., Lu, J., Rodriguiz, R. M., Trotta, N. C., Peca, J., Ding, J.-D., Feliciano, C., Chen, M., Adams, J. P., Luo, J., et al. (2007) · Nature · doi:10.1038/nature06104 · Cited by 852 · see citing works
Neurobiology of rodent self-grooming and its value for translational neuroscience
Kalueff, A. V., Stewart, A. M., Song, C., Berridge, K. C., Graybiel, A. M., & Fentress, J. C. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.8 · Cited by 852 · see citing works
The myeloid cells of the central nervous system parenchyma
Ransohoff, R. M., & Cardona, A. E. (2010) · Nature · doi:10.1038/nature09615 · Cited by 804 · see citing works
“In particular, mice lacking the homeobox gene Hoxb8 do not have neuroanatomical defects but have pathological grooming behaviour, in a pattern with similarities to obsessive–compulsive disorder in human”
BackgroundBehavioural genetics: A question of grooming
Patterson, M. (2002) · Nature reviews genetics · doi:10.1038/nrg740 · Cited by 769
Transgenic mice with hematopoietic and lymphoid specific expression of Cre
de Boer, J., Williams, A., Skavdis, G., Harker, N., Coles, M., Tolaini, M., Norton, T., Williams, K., Roderick, K., Potocnik, A. J., et al. (2003) · European Journal of Immunology · doi:10.1002/immu.200310005 · Cited by 739 · see citing works
Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century
Capecchi, M. (2005) · Nature reviews genetics · doi:10.1038/nrg1619 · Cited by 723 · see citing works
Self-citationThe role of immune dysfunction in the pathophysiology of autism
Onore, C., Careaga, M., & Ashwood, P. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.08.007 · Cited by 635 · see citing works
MicroRNAs and their regulatory roles in animals and plants
Zhang, B., Wang, Q., & Pan, X. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20869 · Cited by 553 · see citing works
Deletion of Selenoprotein P Alters Distribution of Selenium in the Mouse*
Hill, K., Zhou, J.-D., McMahan, W. J., Motley, A., Atkins, J., Gesteland, R., & Burk, R. F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300755200 · Cited by 469 · see citing works
Hematopoietic origin of pathological grooming in Hoxb8 mutant mice
Chen, S.-K., Tvrdik, P., Peden, E., Cho, S., Wu, S., Spangrude, G., & Capecchi, M. R. (2010) · Cell · doi:10.1016/j.cell.2010.03.055 · Cited by 450 · see citing works
“Hoxb8 Cell Lineage Gives Rise to Brain Microglia The expression pattern of Hoxb8 in the adult brain is broad (Greer and Capecchi, 2002).”
BackgroundInfluentialSelf-citationPittenger, C., Bloch, M. H., & Williams, K. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.09.006 · Cited by 426 · see citing works
“…for repetitive or perseverative behaviors (e.g. Eilam et al., 2006; Joel, 2006; Thomas et al., 2009 ), including grooming (Campbell et al., 1999; Greer & Capecchi, 2002; Welch et al., 2007; Shmelkov et al., 2010); anxietyrelated behaviors (e.g. Welch et al., 2007; Shmelkov et al., 2010);…”
BackgroundWoods, D. W., Wetterneck, C. T., & Flessner, C. A. (2006) · Behaviour Research and Therapy · doi:10.1016/j.brat.2005.05.006 · Cited by 381 · see citing works
“Existing animal models (e.g., Bordnick, Thyer, & Ritchie, 1994; Greer & Capecchi, 2002) and neuroimaging studies (e.g., Stein et al., 2002; Swedo et al., 1991; Vythilingum et al., 2002) suggest an underlying pathogenesis involving a disrupted motor habit system and poor inhibitory control.”
BackgroundOntogeny and homeostasis of CNS myeloid cells
Prinz, M., Erny, D., & Hagemeyer, N. (2017) · Nature Immunology · doi:10.1038/ni.3703 · Cited by 391 · see citing works
Factors regulating microglia activation
Kierdorf, K., & Prinz, M. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00044 · Cited by 360 · see citing works
Automated home-cage behavioural phenotyping of mice
Jhuang, H., Garrote, E., Yu, X., Khilnani, V., Poggio, T., Steele, A. D., & Serre, T. (2010) · Nature Communications · doi:10.1038/ncomms1064 · Cited by 274 · see citing works
Berridge, K. C., Aldridge, J. W., Houchard, K. R., & Zhuang, X. (2005) · BMC Biology · doi:10.1186/1741-7007-3-4 · Cited by 309 · see citing works
“It also would be of interest for future studies to examine if other animal models of perseverant grooming behavior, such as Hoxb8lox and D1CT mutant mice, also show any exaggerated serial rigidity features in their fixed action patterns similar to those found here [13,51,53-55,57,65].”
BackgroundResultInduction of innate immune genes in brain create the neurobiology of addiction
Crews, F. T., Zou, J., & Qin, L. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.03.003 · Cited by 313 · see citing works
“Interestingly, microglial dysfunction has been discovered to contribute to obsessive-compulsive behaviors (Greer and Capecchi 2002), consistent with microglia contributing to the neurobiology of addiction.”
BackgroundMicroglial Dysregulation in Psychiatric Disease
Frick, L. R., Williams, K., & Pittenger, C. (2013) · Clinical and Developmental Immunology · doi:10.1155/2013/608654 · Cited by 299 · see citing works
“Ten years ago, mice with a knockout of the HoxB8 gene, a homeobox developmental patterning gene expressed prominently in macrophage-lineage hematopoietic cells, were observed to exhibit excessive grooming behavior; this excessive grooming has been proposed to model OCD symptomatology [103] More recently, HoxB8 mutant…”
BackgroundGrooming analysis algorithm for neurobehavioural stress research.
Kalueff, A., & Tuohimaa, P. (2004) · Brain research. Brain research protocols · doi:10.1016/j.brainresprot.2004.04.002 · Cited by 287 · see citing works
Striatal circuits, habits, and implications for obsessive-compulsive disorder
Burguière, E., Monteiro, P., Mallet, L., Feng, G., & Graybiel, A. M. (2015) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.08.008 · Cited by 286 · see citing works
“These mouse models include the transgenic D1CT-7 model (over-activation of glutamatergic input to the striatum produced by chronic potentiation of dopamine D1-receptor expressing neurons); the Sapap3/Dlgap3 deletion model (defective corticostriatal glutamatergic transmission) and the Slitrk5 deletion model (increased…”
BackgroundWhat's wrong with my mouse model?
Kalueff, A. V., Wheaton, M., & Murphy, D. L. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.01.023 · Cited by 285 · see citing works
“Thus, a new class of animal modls related to anxiety/depression and obsessive–compulsive omains, could be developed based on phenomenological, thological, physiological and pharmacogenetic paradigms of nimal OCD-like behaviors [4,63,117,132,173,223,231].”
BackgroundKalueff, A., & Tuohimaa, P. (2005) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2004.10.001 · Cited by 284 · see citing works
Animal models of restricted repetitive behavior in autism.
Lewis, M., Tanimura, Y., Lee, L. W., & Bodfish, J. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.08.023 · Cited by 270 · see citing works
“Compulsive grooming leading to hair removal and self-inflicted wounds has been identified as a major behavioral phenotype of the Hoxb8 homozygous mutant mouse [21].”
BackgroundGrant, J. E., & Chamberlain, S. R. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2016.15111432 · Cited by 252 · see citing works
“Markedly elevated grooming is exhibited in three models in particular: the Hoxb8 knockout mouse (34), the Sapap3 knockout mouse (35), and the Slitrk5 knockout mouse (36).”
BackgroundKierdorf, K., & Prinz, M. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90602 · Cited by 283 · see citing works
“For example, homeobox protein B8–deficient (Hoxb8deficient) mice develop extensive grooming behavior with hair loss and skin lesions similar to the human OCD spectrum disorder trichotillomania (79).”
BackgroundThe pathophysiology of restricted repetitive behavior
Lewis, M. H., & Kim, S. (2009) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-009-9019-6 · Cited by 233 · see citing works
“Compulsive grooming leading to hair removal and selfinflicted wounds has been identified as a major behavioral phenotype of the Hoxb8 homozygous mutant mouse [156] and the Sapap3 KO mouse [104].”
BackgroundAnalyzing grooming microstructure in neurobehavioral experiments
Kalueff, A., Aldridge, J., Laporte, J., Murphy, D., & Tuohimaa, P. (2007) · Nature Protocols · doi:10.1038/nprot.2007.367 · Cited by 232 · see citing works
“Spruijt, B.M., Welbergen, P., Brakkee, J. & Gispen, W.H. Behavioral changes in ACTH-(1-24)-induced excessive grooming in aging rats.”
BackgroundGrant, J., Odlaug, B., Chamberlain, S., Keuthen, N., Lochner, C., & Stein, D. J. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.12040508 · Cited by 214 · see citing works
Overall, K. L., & Dunham, A. E. (2002) · Journal of the American Veterinary Medical Association · doi:10.2460/javma.2002.221.1445 · Cited by 206 · see citing works
Trichotillomania: A current review.
Duke, D., Keeley, M. L., Geffken, G., & Storch, E. (2010) · Clinical Psychology Review · doi:10.1016/j.cpr.2009.10.008 · Cited by 205 · see citing works
“Considering an ethological model, Greer and Capecchi (2002) reported that mice with a mutation of the hoxb8 neurodevelopmental gene, demonstrated unusual grooming behaviors that included hairpulling.”
BackgroundBrimberg, L., Benhar, I., Mascaro-Blanco, A., Alvarez, K., Lotan, D., Winter, C., Klein, J., Moses, A. E., Somnier, F. E., Leckman, J. F., et al. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.56 · Cited by 202 · see citing works
“The assessment of induced-grooming followed that of Greer and Capecchi (2002) (also see Supplementary Methods online).”
BackgroundMicroRNAs: A new class of gene regulators
Guarnieri, D. J., & Dileone, R. (2008) · Annals of Medicine · doi:10.1080/07853890701771823 · Cited by 202 · see citing works
Garner, J. P. (2014) · ILAR Journal · doi:10.1093/ilar/ilu047 · Cited by 222 · see citing works
Is obsessive-compulsive disorder an anxiety disorder?
Bartz, J. A., & Hollander, E. (2006) · Progress in Neuro-psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2005.11.003 · Cited by 187 · see citing works
“Greer and Capecchi (2002) found that mutations on the hoxb8 gene in mice were associated with excessive grooming and hair removal—behaviors that are characteristic of trichotillomania.”
BackgroundThe evolution of parasite-defence grooming in ungulates
Mooring, M., Blumstein, D., & Stoner, C. (2004) · Biological Journal of the Linnean Society · doi:10.1111/j.1095-8312.2004.00273.x · Cited by 187 · see citing works
“Grooming behaviour is under the influence of multiple genes, including the Hoxb8 gene, which, when disrupted, leads to excessive self-grooming and allogrooming in mice (Greer & Capecchi, 2002), but other genes that influence this complex behaviour are currently unknown.”
BackgroundMehta, M. V., Gandal, M. J., & Siegel, S. J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026077 · Cited by 182 · see citing works
“However, both marble burying and self-grooming assays have also been shown to be sensitive to anxiety [43,44], although there is some controversy as to which behavior each task is most sensitive [25,45].”
BackgroundHoxb13 is required for normal differentiation and secretory function of the ventral prostate
Economides, K. D., & Capecchi, M. (2003) · Development · doi:10.1242/dev.00432 · Cited by 179 · see citing works
“…due to the silencing of the target locus and nearby genes by the methylation of the lacZ bacterial gene as has been previously reported (Thorey et al., 1993; Cohen-Tannoudji et al., 2000; K. D. Economides and M. R. Capecchi 2063The function of Hoxb13 in the prostate Greer and Capecchi, 2002).”
Self-citationQuinonez, S. C., & Innis, J. (2014) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2013.10.012 · Cited by 173 · see citing works
“These include, but are not limited to, the multi-organ malformations that accompany Hoxa3 loss-of-function, the hematologic abnormalities ofHoxb4orHoxa9 loss-of-function, the esophageal dysfunction anddisorganized throat musculature of Hoxc4 loss-of-function and the pathologic excessive grooming behavior ofHoxb8mutant…”
BackgroundCurrent animal models of obsessive compulsive disorder: a critical review
Joel, D. (2006) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2005.11.006 · Cited by 168 · see citing works
“Hoxb8 mutants as a model of the OC-spectrum disorder, trichotillomania Greer and Capecchi (2002) reported that mice with disruptions of Hoxb8 show excessive grooming compared to control litermates, manifested in longer time spent grooming, more frequent initiation of grooming, the presence of hair…”
BackgroundmicroRNAs: a new emerging class of players for disease diagnostics and gene therapy
Zhang, B., & Farwell, M. A. (2007) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2007.00196.x · Cited by 141 · see citing works
“For example, miR196 directly cleaves the mRNA of HOXB8 [47–49], which plays important role in animal development [50–53].”
Ting, J. T., & Feng, G. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.04.010 · Cited by 143 · see citing works
“In 2002, the Capecchi lab reported that Hoxb8lox mutant mice exhibited compulsive grooming and fur loss with 100% penetrance [27].”
BackgroundCompulsive behavior in the 5-HT2C receptor knockout mouse
Chou-Green, J. M., Holscher, T. D., Dallman, M. F., & Akana, S. F. (2003) · Physiology & Behavior · doi:10.1016/s0031-9384(03)00047-7 · Cited by 143 · see citing works
“Excessive lever pressing [22], excessive grooming [23], running [24], and schedule-induced polydipsia [25] have also been described as possible animal models of OCD.”
BackgroundMicroglia: Key Elements in Neural Development, Plasticity, and Pathology
Eyo, U. B., & Dailey, M. E. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9434-z · Cited by 138 · see citing works
“In early studies, the authors concluded that, although Hoxb8 is expressed in both the central and peripheral nervous system, the basis of the excessive grooming phenotype was more than likely aberrations in the central rather than peripheral nervous system (Greer and Capecchi 2002).”
BackgroundAngoa-Perez, M., Kane, M. J., Briggs, D. I., Sykes, C. E., Shah, M. M., Francescutti, D., Rosenberg, D. R., Thomas, D. M., & Kuhn, D. M. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07739.x · Cited by 133 · see citing works
“Other constitutive knockout mouse models such as Slitrk5 (Shmelkov et al. 2010), Sapap3 (Welch et al. 2007), Hoxb8 (Greer and Capecchi 2002) and Shank3 (Peca et al. 2011) express compulsive behaviors but primarily in the form of excessive, self-injurious grooming.”
BackgroundKas, M. J., Glennon, J. C., Buitelaar, J., Ey, E., Biemans, B., Crawley, J., Ring, R. H., Lajonchere, C., Esclassan, F., Talpos, J., et al. (2014) · Psychopharmacology · doi:10.1007/s00213-013-3268-5 · Cited by 132 · see citing works
“Hoxb8 overexpression/ Trichotillomania Hoxb8 homozygous mutant mice Excessive grooming (Greer and Capecchi 2002)”
BackgroundTrichotillomania: neurobiology and treatment
Chamberlain, S. R., Odlaug, B. L., Boulougouris, V., Fineberg, N. A., & Grant, J. E. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.02.002 · Cited by 126 · see citing works
“…not spontaneous , for example resulting from pharmacological or genetic manipulations (Yadin et al., 1991; Ichimaru et al., 1995; Szechtman et al., 1998; Campbell et al., 1999a,b; Joel and Avisar, 2001; Greer and Capecchi, 2002; Chou-Green et al., 2003; Berridge et al., 2005; Tsaltas et al., 2005).”
BackgroundKrabbe, G., Minami, S., Etchegaray, J. I., Taneja, P., Djukic, B., Davalos, D., Le, D., Lo, I., Zhan, L., Reichert, M. C., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1700477114 · Cited by 132 · see citing works
“Alterations in microglia/myeloid cells have been implicated in pathological grooming, but the underlying mechanism is unclear (28, 29).”
BackgroundHair barbering in mice: implications for neurobehavioural research.
Kalueff, A. V., Minasyan, A., Keisala, T., Shah, Z., & Tuohimaa, P. (2006) · Behavioural Processes · doi:10.1016/j.beproc.2005.09.004 · Cited by 126 · see citing works
Schaun Korff, A., & Harvey, B. H. (2006) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2006.02.007 · Cited by 123 · see citing works
Glutamatergic Synaptic Dysfunction and Obsessive-Compulsive Disorder
Ting, J. T., & Feng, G. (2008) · Current Chemical Genomics · doi:10.2174/1875397300802010062 · Cited by 121 · see citing works
“To address the role of Hoxb8 in the adult brain, Greer and Capecchi [106] created mice homozygous for a loss-of-function allele of Hoxb8.”
BackgroundHoxc10 and Hoxd10 regulate mouse columnar, divisional and motor pool identity of lumbar motoneurons
Wu, Y., Wang, G., Scott, S. A., & Capecchi, M. R. (2007) · Development · doi:10.1242/dev.009225 · Cited by 108 · see citing works
“2), which we created because the presence of neo can affect the mouse phenotype by altering the expression of nearby genes (Greer and Capecchi, 2002; Manley et al., 2001).”
BackgroundSelf-citationHill, K., Zhou, J.-D., Austin, L. M., Motley, A., Ham, A., Olson, G., Atkins, J., Gesteland, R., & Burk, R. F. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700436200 · Cited by 115 · see citing works
Slitrks as emerging candidate genes involved in neuropsychiatric disorders
Proenca, C. C., Gao, K. P., Shmelkov, S. V., Rafii, S., & Lee, F. S. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.01.001 · Cited by 116 · see citing works
Microglial Dysregulation in OCD, Tourette Syndrome, and PANDAS
Frick, L. R., & Pittenger, C. (2016) · Journal of Immunology Research · doi:10.1155/2016/8606057 · Cited by 111 · see citing works
“An early study reported that knockout of theHoxb8 gene produces compulsive grooming, progressing to hair removal and ultimately to skin lesions [19].”
BackgroundGeorgiadou, G., Tarantilis, P., & Pitsikas, N. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.08.081 · Cited by 108 · see citing works
“n animals is regarded similar to the symptoms of OCD and ther obsessive–compulsive (OC)-spectrum disorders in humans ncluding trichotillomania [6,7].”
BackgroundEstrogen Deficient Male Mice Develop Compulsive Behavior
Hill, R., McInnes, K. J., Gong, E. C. H., Jones, M. E. E., Simpson, E. R., & Boon, W. C. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.01.012 · Cited by 109 · see citing works
Ferrão, Y. A., Miguel, E., & Stein, D. J. (2009) · Psychiatry Research · doi:10.1016/j.psychres.2008.06.008 · Cited by 107 · see citing works
“Candidate genes that seemworth pursuing include hoxB8 (Greer and Capecchi, 2002) and SLITRK1 (abnormalities of which led to trichotillomania in one patient) (Abelson et al., 2005; Zuchner et al., 2006).”
BackgroundBordt, E. A., Ceasrine, A. M., & Bilbo, S. D. (2020) · Glia · doi:10.1002/glia.23753 · Cited by 118 · see citing works
“…idea that microglia may traffic via alternative routes from the fetal yolk sac to the brain gained support from the finding that a proportion of microglia in the brain are derived from fetal yolk sac cells expressing the homeobox 8 (Hoxb8) gene (Chen et al., 2010; Greer & Capecchi, 2002).”
BackgroundThe Mouse Who Couldn't Stop Washing: <i>Pathologic Grooming in Animals and Humans</i>
Feusner, J. D., Hembacher, E., & Phillips, K. A. (2009) · CNS Spectrums · doi:10.1017/s1092852900023567 · Cited by 106 · see citing works
Kalueff, A., & Tuohimaa, P. (2005) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.11.010 · Cited by 106 · see citing works
Microglia in the developing brain: from immunity to behaviour
Schlegelmilch, T., Henke, K., & Peri, F. (2010) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2010.08.004 · Cited by 99 · see citing works
Hollander, E., Kim, S., Khanna, S., & Pallanti, S. (2007) · CNS Spectrums · doi:10.1017/s1092852900002467 · Cited by 102 · see citing works
Developing better and more valid animal models of brain disorders.
Stewart, A., & Kalueff, A. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.12.024 · Cited by 101 · see citing works
“Manic phenotype (hyperactivity, increased sexual behavior) [20]”
Grey matter abnormalities in trichotillomania: morphometric magnetic resonance imaging study
Chamberlain, S., Menzies, L., Fineberg, N., Campo, N. D., Suckling, J., Craig, K., Müller, U., Robbins, T., Bullmore, E., & Sahakian, B. (2008) · The British journal of psychiatry : the journal of mental science · doi:10.1192/bjp.bp.107.048314 · Cited by 97 · see citing works
Cognition, motivation, emotion and action: a dynamic and vulnerable interdependence
Toates, F. (2004) · Applied Animal Behaviour Science · doi:10.1016/j.applanim.2004.02.010 · Cited by 96 · see citing works
Behavioral and neural effects of intra-striatal infusion of anti-streptococcal antibodies in rats
Lotan, D., Benhar, I., Alvarez, K., Mascaro-Blanco, A., Brimberg, L., Frenkel, D., Cunningham, M., & Joel, D. (2014) · Brain, behavior, and immunity · doi:10.1016/j.bbi.2014.02.009 · Cited by 94 · see citing works
“The assessment of induced-grooming was carried out as previously described (Brimberg et al., 2012; Greer and Capecchi, 2002).”
MethodLifting the Veil on Trichotillomania
Chamberlain, S. R., Menzies, L. A., Sahakian, B. J., & Fineberg, N. A. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.4.568 · Cited by 98 · see citing works
“Greer JM, Capecchi MR: Hoxb8 is required for normal grooming behavior in mice.”
BackgroundAn A-B-C Model of Habit Disorders: Hair-Pulling, Skin-Picking, and Other Stereotypic Conditions
Stein, D. J., Chamberlain, S., & Fineberg, N. (2006) · CNS Spectrums · doi:10.1017/s1092852900014978 · Cited by 94 · see citing works
Microglia: dismantling and rebuilding circuits after acute neurological injury
Ziebell, J. M., Adelson, P. D., & Lifshitz, J. (2015) · Metabolic Brain Disease · doi:10.1007/s11011-014-9539-y · Cited by 84 · see citing works
“For example, microglia are the only brain cells to express Hoxb8, for which mice lacking Hoxb8 exhibit obsessive grooming behavior (Greer and Capecchi 2002).”
Genetics of obsessive-compulsive disorder and related disorders
Browne, H. A., Gair, S. L., Scharf, J. M., & Grice, D. E. (2014) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2014.06.002 · Cited by 92 · see citing works
From compulsivity to compulsion: the neural basis of compulsive disorders
Robbins, T. W., Banca, P., & Belin, D. (2024) · Nature reviews. Neuroscience · doi:10.1038/s41583-024-00807-z · Cited by 99 · see citing works
Elaborate ornaments are costly to maintain: evidence for high maintenance handicaps
Walther, B., & Clayton, D. H. (2005) · Behavioral Ecology · doi:10.1093/beheco/arh135 · Cited by 90 · see citing works
“However, since the amount of time devoted to maintenance has a strong genetic basis (Greer and Capecchi, 2002), it is likely that the relative grooming rates of different wild species will be reflected in captive individuals of these same species, making it possible to test the high maintenance…”
BackgroundNeural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders
Gandhi, T., & Lee, C. C. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.592710 · Cited by 94 · see citing works
Mouse models of frontotemporal dementia
Roberson, E. D. (2012) · Annals of Neurology · doi:10.1002/ana.23722 · Cited by 97 · see citing works
Current animal models of obsessive compulsive disorder: an update
Albelda, N. S., & Joel, D. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.08.070 · Cited by 81 · see citing works
“The first class includes D1CT-7 transgenic mice (Campbell et al., 1999a–c; McGrath et al., 1999a,b; Nordstrom and Burton, 2002), Hoxb8 mutant mice (Greer and Capecchi, 2002), 5-HT2c knockout mice (Chou-Green et al., 2003), dopamine transporter knockdown mice (Berridge et al., 2005), aromatase…”
BackgroundBehavior Therapy for Pediatric Trichotillomania: A Randomized Controlled Trial
Franklin, M., Edson, A. L., Ledley, D. A., & Cahill, S. (2011) · Journal of the American Academy of Child and Adolescent Psychiatry · doi:10.1016/j.jaac.2011.05.009 · Cited by 84 · see citing works
Genetics of obsessive-compulsive disorders: new findings and challenges.
Grados, M., Walkup, J., & Walford, S. (2003) · Brain & development (Tokyo. 1979) · doi:10.1016/s0387-7604(03)90010-6 · Cited by 84 · see citing works
Feygin, D. L., Swain, J. E., & Leckman, J. F. (2006) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2006.01.009 · Cited by 89 · see citing works
Learning From Animal Models of Obsessive-Compulsive Disorder
Monteiro, P., & Feng, G. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.04.020 · Cited by 79 · see citing works
“- HOXB8 Another interesting hypothesis concerning OCD etiology comes from genetic deletion of the Hoxb8 gene in mice, which suggests a link between the immune system and OCD expression [88].”
BackgroundThe signal attenuation rat model of obsessive–compulsive disorder: a review
Joel, D. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0387-2 · Cited by 78 · see citing works
“2002), the Hoxb8 mutants as a model of the OC-spectrum disorder trichotillomania (Greer and Capecchi 2002), the 5-HT2c receptor knockout mouse as a model of compulsive”
BackgroundContrasting grooming phenotypes in C57Bl/6 and 129S1/SvImJ mice.
Kalueff, A., & Tuohimaa, P. (2004) · Brain Research · doi:10.1016/j.brainres.2004.09.001 · Cited by 79 · see citing works
Lee, S. F. (2003) · Gene Expression Patterns · doi:10.1016/s1567-133x(03)00113-3 · Cited by 77 · see citing works
“The orbitofrontal cortex, cingulate cortex and the caudoputamen are implicated in compulsive behavior, which is a common finding in PWS (Dykens et al., 1996; Graybiel and Rauch, 2000; Greer and Capecchi, 2002; Saxena et al., 1998; Warnock and Kestenbaum, 1992; Whitman and Accardo, 1987).”
BackgroundFrick, L. R., Rapanelli, M., Abbasi, E., Ohtsu, H., & Pittenger, C. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.07.002 · Cited by 90 · see citing works
Reduced Brain White Matter Integrity in Trichotillomania
Chamberlain, S. R., Hampshire, A., Menzies, L. A., Garyfallidis, E., Grant, J. E., Odlaug, B. L., Craig, K. J., Fineberg, N. A., & Sahakian, B. J. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.109 · Cited by 76 · see citing works
“Cluster 2 had peak coordinates of [20, 26, 26] and a size of 553 voxels and comprised the bilateral an-”
BackgroundCorticostriatal circuit defects in Hoxb8 mutant mice
Nagarajan, N., Jones, B. W., West, P. J., Marc, R. E., & Capecchi, M. R. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.180 · Cited by 93 · see citing works
“Targeted disruption of Hoxb8 gene causes brain specific 6,7 compulsive hair removal behavior closely resembling the OCD spectrum disorder Trichotillomania in humans 21 .”
Self-citationAbnormal repetitive behaviours: shared phenomenology and pathophysiology
Muehlmann, A. M., & Lewis, M. H. (2012) · Journal of Intellectual Disability Research · doi:10.1111/j.1365-2788.2011.01519.x · Cited by 76 · see citing works
Animal models of obsessive–compulsive disorder: utility and limitations
Alonso, P., López‐Solà, C., Real, E., Segalàs, C., & Menchón, J. M. (2015) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s62785 · Cited by 84 · see citing works
“55 5-HT2c 5-HT2c receptor KO mouse 5-HT2c receptor KO mice were described by Chou-Green et al to display compulsive-like behavior, comprising more chewing of nonnutritive clay, a distinct pattern of neat chewing of plastic-mesh screen, and reduced habituation of head-dipping activity.”
Loss of Hoxb8 alters spinal dorsal laminae and sensory responses in mice
Holstege, J., de Graaff, W. D., Hossaini, M., Cano, S. C., Jaarsma, D., van den Akker, E. V. D., & Deschamps, J. (2008) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0802176105 · Cited by 73 · see citing works
“The disorganized lamina I neurons might secondarily aberrantly contact their projection targets in the brain, indirectly involving higher brain centers in the phenotype, thus in agreement with the conclusion by Greer and Capecchi (12) in their study of another Hoxb8 mutant allele.”
BackgroundResultInfluentialUnderstanding and treating trichotillomania: what we know and what we don't know.
Woods, D. W., Flessner, C., Franklin, M., Wetterneck, C. T., Walther, M. R., Anderson, E. R., & Cardona, D. (2006) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2006.02.009 · Cited by 72 · see citing works
“Although a specific TTM gene has not been identified in humans, a genetic basis for TTM has been suggested [17,20,21].”
BackgroundWhite Matter Abnormalities in Skin Picking Disorder: A Diffusion Tensor Imaging Study
Grant, J. E., Odlaug, B. L., Hampshire, A., Schreiber, L. R. N., & Chamberlain, S. R. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.241 · Cited by 79 · see citing works
Estanislau, C. R., Veloso, A. W. N., Filgueiras, G. B., Maio, T. P., Dal-Cól, M. L. C., Cunha, D. C., Klein, R. M., Carmona, L. F., & Fernández‐Teruel, A. (2019) · Physiology & Behavior · doi:10.1016/j.physbeh.2019.112585 · Cited by 75 · see citing works
Sundberg, J. P., Taylor, D., Lorch, G., Miller, J., Silva, K., Sundberg, B., Roopenian, D., Sperling, L. C., Ong, D. E., King, L. E., et al. (2010) · Veterinary Pathology-Supplement · doi:10.1177/0300985810379431 · Cited by 67 · see citing works
“Genetically engineered mice with Hoxb8 null mutations (Hoxb8) develop severe trichotillomania as their primary phenotype, which may be a primary or complicating part of this disease in C57BL/6 mice.(13) As Hoxb8 is expressed primarily in the brain, RNA was tested from this organ.”
BackgroundImmunological Dysfunction in Tourette Syndrome and Related Disorders
Hsu, C., Wong, L., & Lee, W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020853 · Cited by 76 · see citing works
“Hoxb8-knockout mice developed excessive grooming behavior and hair loss [113,114].”
BackgroundUsing mice to model Obsessive Compulsive Disorder: From genes to circuits
Ahmari, S. E. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.11.009 · Cited by 68 · see citing works
“Mice began to over-groom themselves, and persisted in this behavior even after developing severe facial and body lesions (Greer and Capecchi, 2002).”
BackgroundA novel, multiple symptom model of obsessive-compulsive-like behaviors in animals.
Andersen, S., Greene-Colozzi, E. A., & Sonntag, K. C. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.05.011 · Cited by 65 · see citing works
Mouse Models of Autism: Testing Hypotheses About Molecular Mechanisms
Roullet, F., & Crawley, J. N. (2011) · Current topics in behavioral neurosciences · doi:10.1007/7854_2010_113 · Cited by 65 · see citing works
“Sapap3 (Welch et al. 2007) and Hoxb8 knockout mice (Greer and Capecchi 2002) exhibit extreme self-grooming that leads to hair loss and skin injuries.”
BackgroundAdult zebrafish in CNS disease modeling: a tank that's half-full, not half-empty, and still filling
Мешалкина, Д. А., Kysil, E. V., Warnick, J. E., Demin, K. A., & Kalueff, A. V. (2017) · Lab Animal · doi:10.1038/laban.1345 · Cited by 70 · see citing works
- Authors
- Greer, J. M., & Capecchi, M. R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Capecchi, Mario R.
- ORCID
- Capecchi, Mario R.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 33
- Issue
- 1
- Pages
- 23-34
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2155060440
- Cited by
- 401
- References
- 46
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 14 · 2023: 9 · 2022: 11 · 2021: 22 · 2020: 5 · 2019: 15 · 2018: 14 · 2017: 22 · 2016: 17 · 2015: 19 · 2014: 20 · 2013: 18 · 2012: 25
- FWCI
- 19.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 4215 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Hoxb8, grooming, obsessive-compulsive disorder, trichotillomania, hair removal
- MeSH terms
- Aging, Alleles, Animals, Animals, Newborn, Behavior, Animal, Bone and Bones, Brain, Brain Chemistry, Disease Models, Animal, Female, Genotype, Grooming, Male, Mice, Neurologic Mutants, Nerve Net, Obsessive-Compulsive Disorder, Phenotype, RNA, Messenger, Skin, Mice, Knockout, Homeodomain Proteins, Mice
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