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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 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]
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Cites
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Items 301–336 of 336
Trichotillomania (Compulsive Hair Pulling) and Compulsive Skin Picking
Fineberg, N., Grant, J., Odlaug, B., Boulougouris, V., & Chamberlain, S. (2010) · Elsevier eBooks · doi:10.1016/b978-0-08-045396-5.00184-6 · Cited by 1
The Genetics of Obsessive–Compulsive Disorder
Grados, M. A., & Dang, R. (2009) · Springer eBooks · doi:10.1007/978-90-481-2298-1_9 · Cited by 8
Conservation of Phenotypes in the Roman High- and Low-Avoidance Rat Strains After Embryo Transfer
Río-Álamos, C., Gerbolés, C., Tapias-Espinosa, C., Sampedro-Viana, D., Oliveras, I., Sánchez-González, A., Cañete, T., Blázquez, G., López, M. D. M., Baldellou, C., et al. (2017) · Behavior Genetics · doi:10.1007/s10519-017-9854-2
“In addition, there is evidence indicating a high sensitivity of self-grooming (and self-grooming sequencing) to genetic influences (Kalueff et al. 2016; see also; Greer and Capecchi 2002), and it has been shown that selfgrooming can be bidirectionally affected by psychological stress (Fernández-Teruel and Estanislau 2…”
BackgroundA Gut‐Brain Axis Underlying Succinate‐Associated Compulsive‐Like Behavior
Li, Y., Zhang, Y.-D., Wang, W., Wu, X., Li, D., Gong, X., Tian, F., Dai, M., Gao, J., Zheng, Z., et al. (2026) · Advanced Science · doi:10.1002/advs.77836
“This transgenic line is a well-established model of trichotillomania, an OCD-spectrum disorder, exhibiting excessive anxiety and compulsive-like behaviors [ 37, 38 ].”
A Microglial Regulatory Program Linked to Neuropsychiatric DisordersPreprint
Tränkner, D., Johnson, A. P., Williams, M. E., & Rothenfluh, A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.27.747643
“Germline disruption of Hoxb8 causes pathological overgrooming and anxiety-like behavior despite developmental abnormalities largely restricted to sensory circuits of the dorsal spinal cord (Chen et al., 2010; Greer & Capecchi, 2002; Trankner et al., 2019).”
Zhang, N., Xue, L., Chai, S., Wang, T., Jiang, Y., Lei, J., & Wei, H. (2026) · Neuroscience · doi:10.1016/j.neuroscience.2026.07.034
Miller, E. C., Bork, T., McCall, C., Allen, K., Hoover, C., Nemeth, C., Eby, A., Borrelli, H., Vandiver, V., Trollip, L., et al. (2026) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2026.111871
Zheng, X., Liu, L., Niu, Z., Li, Y., Liu, Z., Shu, X., Wang, H., Xu, B., Wang, Y., Chen, J., et al. (2026) · Poultry Science · doi:10.1016/j.psj.2026.107232
“HOXB8 knockout induces compulsive grooming and anxiety in mice, recapitulating symptoms of human obsessive-compulsive disorder and trichotillomania (Greer and Capecchi, 2002).”
Novel mouse line with D277N mutation in the Plau gene displays autism spectrum disorder-like traits
Karagyaur, M., Averina, O., Bozov, K., Dzhauari, S., Priymak, A., Khaybullina, R., Permyakov, O., Popov, V., Grigorieva, O., Illarionova, M., et al. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1762737
“On the other hand, the propensity for stereotypy in these mice may not be present, as this behavioral disorder may be due to dysfunction of other/additional genes (e.g., Hoxb8 , Slc1a1 , Sapap3 , Slitrk5 , Spred2 or PlxnA3 ) (Greer and Capecchi, 2002; Zike et al., 2017; Karagyaur et al., 2025).”
Trichotillomania and trichophagia leading to gastric perforation in an adolescent: A case report
da Silva, B. C., & Cardoso, I. (2026) · Neuropsychiatrie de l'enfance et de l'adolescence · doi:10.1016/j.neurenf.2026.02.011
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Cordeiro, R. C., Scaini, G., & Quevedo, J. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02511-x · Cited by 1
“A growing body of research indicates that a targeted disruption/mutation of the Hoxb8 gene or ablation of a microglial subpopulation induced chronic anxiety and OCSD-like behavior, compulsive pathological hair pulling, to the point of showing lesions at the sites of overgrooming [5, 6].”
Animal models of Obsessive-Compulsive Disorder (OCD)
Nabizadeh, M., & Ahmadi, F. (2022) · Journal of Neurodevelopmental Cognition · doi:10.52547/jncog.2022.103445
“and at the moment, five OCD mouse models are included in genetic animal models as: the D1CT-7 transgenic mouse model of comorbid OCD and TS (Tourette’s syndrome), the mutant mouse Hoxb8 model of trichotillomania, the SAP90/PSD95-associated protein 3 (SAPAP3), the 5-HT2C receptor knockout mouse model of OCD and the DAT…”
Horii‐Hayashi, N., Masuda, K., Kato, T., Kobayashi, K., & Nishi, M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.01.514798
“HoxB8 (46), Slitrk5 (47), Sapap3 (48), and aromatase (49) as well as an optogenetic model stimulating the OFC-Str pathway (50).”
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Hincapié, J. A., Suárez, M. L. C., & Góngora, M. E. (2022) · CES Medicina Veterinaria y Zootecnia · doi:10.21615/cesmvz.6776 · Cited by 1
Olusoji, E. B., Adesina, M., & Kanmodi, K. K. (2019) · The APRN and PA’s Complete Guide to Prescribing Drug Therapy · doi:10.1891/9780826179340.0394
“In an animal research work, Greer and Capecchi (2002) reported that mice with mutation of the hoxb8 neurodevelopmental gene showed aberrant grooming behaviour including hair pulling.”
BackgroundThe Molecular Genetics of Obsessive-Compulsive and Related Disorders
Kohlrausch, F. B. (2018) · Cambridge University Press eBooks · doi:10.1017/9781108164313.005 · Cited by 1
Body-Focused Repetitive Behaviors
Grant, J. E., & Chamberlain, S. R. (2018) · Cambridge University Press eBooks · doi:10.1017/9781108164313.029
Vayısoğlu, S. (2018) · Journal of Neurology & Stroke · doi:10.15406/jnsk.2018.08.00330
Functions of the transcription factor Lyl-1 in the development of the macrophage lineage
Wang, S. (2017) · theses.fr (ABES) · doi:10.70675/9d04371azfd66z45f0z94b9zee4c34133d89
“By specifically deleting the Hoxb8 gene, Greer and Capecchi found that the resultant knockout mice display excessive (pathological) grooming behavior in an obsessive-compulsive behavioral pattern that lead to hair loss and self-inflicted skin lesions (Greer and Capecchi, 2002).”
de Oliveira, D. M. (2015) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2015.tde-10122015-070134
Obsessive–Compulsive and Related Disorders: Obsessive–Compulsive Disorder and Hoarding Disorder
Pato, M. T., Steketee, G. S., Eisen, J. L., Yip, A. G., & Phillips, K. A. (2015) · Wiley eBooks · doi:10.1002/9781118753378.ch57
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Key to psychological disorder may lie in the immune system
Weaver, J. (2010) · Nature · doi:10.1038/news.2010.268
Syndrome de Gilles de la Tourette : vers le renouveau des maladies neuropsychiatriques
Derkinderen, P. (2008) · La Presse Médicale · doi:10.1016/j.lpm.2006.11.032
Neurobiology and Pharmacotherapy of Obsessive‐Compulsive Disorder
Rapoport, J. L., & Inoff‐Germain, G. (2007) · Wiley eBooks · doi:10.1002/9780470101001.hcn028
Murphy, T. K., Frazier, S., & Kim, S. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-252-6_10 · Cited by 11
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Hilaire, D. S. (2021) · doi:10.54014/pxqs-nzgt
“These mice show OCD-like behaviors through excessive grooming, but it is unclear to which extent these findings can be translatable 14 and informative about OCD in humans (Greer & Capecchi, 2002).”
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Galop, B. (2020) · UKnowledge (University of Kentucky) · doi:10.13023/etd.2020.208
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Molecular Genetics and Metabolism
Quinonez, S. C., & Innis, W. (2014) · doi:10.1016/s1096-7192(14)00030-4
Trastorno obsesivo compulsivo y trastornos relacionados
Stewart, E., Lafleur, D., Dougherty, D. D., Wilhelm, S., Keuthen, N., & Jenike, M. (2014) · doi:10.1176/appi.books.9780890425657.x06-es
Tiermodelle für Zwangsstörungen
Winter, C. (2011) · Springer eBooks · doi:10.1007/978-3-642-19844-1_26
Metadata
- 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 › Dermatology › 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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