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Barbering (excessive grooming causing hair loss) in mice resembles trichotillomania (uncontrollable hair pulling) in humans in several respects and may be a useful model of trichotillomania, especially for investigating the complex genetic and environmental interactions
Our interest in systemic lupus erythematosus led us to develop an animal model of lupus by immunising rabbits or mice with peptides that are targets of autoimmune sera from people with lupus. Animals immunised with these peptides developed autoimmunity to the entire Ro ribonucleoprotein as well as to other autoantigens.1-3 During this study, we observed the loss of facial hair in a group of five experimental mice, possibly a sign of alopecia, a symptom of lupus. When we observed the characteristics of the hair loss and the fact that one of the mice had not lost her facial hair whereas the other four had, we realised that this was a clear case of “barbering.”
Fur and whisker trimming by laboratory mice is referred to as “barbering.” Laboratory mice housed in groups are frequently found with their facial hair and whiskers removed (figure). In one study facial alopecia was found in three of four adult female Fisher 344 rats that shared a cage for two months.4 The hairless areas were non-pruritic and without any association with pathogenic skin bacteria, dermatophytes, or ectoparasites. The authors found that when the unaffected rat was placed with a different set of rats, facial alopecia became evident in those animals within six days, and the hair of the original cagemates grew back within 21 days. Thus the alopecia was found to be caused by a dominant female “barber.”4
In another study the barbering process was videotaped in pairs of C57BL6 mice containing a dominant barber and a passive recipient, which showed that dominant mice were responsible for barbering the hair of the recipient (the “Dalila effect”). Barbering occurred only during mutual grooming, when one member of a mouse pair removed the whiskers of the other by grasping individual whiskers with the incisors and plucking them out. The recipients seemed passive in accepting the presumably painful procedure and even pursued the barber for further grooming. It was found that the barbers were heavier than the recipients, but with no apparent difference in brain weight.5 Barbering occurs only occasionally in group housed laboratory mice, but occurs almost invariably in the A2G strain of mice.6 This tendency progresses with age in these animals. Over three quarters of cages with two or three mice have one or more active barbers by the time the mice are 60 days old.7
Diseases in animals that develop spontaneously in a limited subpopulation can serve as models of human disease as they provide ways to investigate the interaction of a wide range of environmental and biological processes. In contrast, the aetiology of experimentally induced animal models is inherently fixed.8 The abnormal barbering seen in mice resembles the compulsive hair plucking in humans known as trichotillomania and could serve as an animal model of this disease because the barbering mice pluck focused areas of hair, barbering is female biased, onset of barbering occurs during puberty, and the aetiological factors included genetic background and reproductive status. Trichotillomania also has important similarities with an avian disorder known as feather picking in terms of behaviour and proposed aetiologies.9
Excessive pathological grooming in humans is a neuropsychiatric condition associated with obsessive-compulsive disorder.10 Trichotillomania, a disorder involving the uncontrollable pulling of one's own hair that can lead to baldness and loss of eyebrow hair, is often characterised as falling within the spectrum of obsessive-compulsive disorders. However, in spite of overlapping phenomenology, there are important differences. Firstly, there is the absence of obsessive rumination in trichotillomania. Hair pulling in trichotillomania is not in response to obsessive thoughts (such as worry about harm to others or self) but to an irresistible urge coupled with the promise of gratification associated with pulling of hair, in contrast to compulsions in obsessive-compulsive disorder.11 Secondly, the ego-dystonic compulsive act is absent, and individuals tend not to substitute other compulsive rituals after prevention of hair pulling. Thus, patients with trichotillomania usually present only with hair pulling without evolution to non-self injurious compulsive rituals, unlike patients with obsessive-compulsive disorder, whose symptoms change over time in terms of focus and severity (such as from checking locks, stoves, appliances, etc, to washing hands).12,13
Trichotillomania, first described in 1889,14 is classified in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) as an “impulse-control disorder not elsewhere specified.”15 The prevalence of trichotillomania is 0.6-1.6% when DSM-IV criteria are used.16 The number of hairs extracted, time spent in pulling hair, and the pattern of pulling vary considerably among sufferers. Those who engage in these kinds of activity also indulge in other repetitive body focused behaviours such as nail biting, tongue chewing, head banging, and cheek chewing.17,18 Hair pulling has also been diagnosed in early childhood, and this has been conceptualised as an anxiety disorder.19
Obsessive-compulsive behaviour disorder in humans is often characterised by excessive behaviours dealing with cleanliness, including grooming. Mice homozygous for a loss of function mutation in the Hoxb8 gene show excessive pathological grooming that leads to removal of hair from their own body as well as barbering cagemates and self infliction of wounds in groomed areas.20 Hoxb8 is a member of the mammalian Hox (Homeo-box-containing) complex, comprising a group of 39 transcription factors. The Hox genes function in enabling embryonic development, hair formation in adult mice, and maturation of breast tissue in female mice.20
In the case of barbering in mice two agents are needed, the dominant barber and the passive recipient—whereas in human trichotillomania these roles are ostensibly combined. While those who pull hair may be a clinically heterogeneous group there is some consensus that those with trichotillomania fall into one of two categories—focused (those who experience mounting anxiety before hair pulling and obtain subsequent relief) or automatic (those who pull their hair when distracted).21 In the case of barbering the recipient mouse that pursues the barber is analogous to the automatic variant, since the regrowth of hair (and, by inference, lack of hair pulling) in the barber's absence is more or less incompatible with the drive to relieve tension that forms the basis of focused trichotillomania. However, individually housed Hoxb8 mutants groom themselves excessively and have large bald patches on their ventral and lateral surfaces,20 thus showing similarity to trichotillomania. All Hoxb8 mutants have shown normal reactions to heat, cold, pain, and pressure. They do not differ from normal mice in most behaviours except for grooming, hair pulling, and self mutilation.
The excessive grooming behaviour linked to the loss of Hoxb8 function is clinically interesting on account of its possible relation to the aetiology of human trichotillomania, especially because the mouse and human pathologies are similar. Trichotillomania may arise as a result of the misregulation of an innate self grooming behaviour that results in excessive repetition. It would be interesting to find out whether subsets of human patients with trichotillomania have defects in the Hoxb8 gene or in the paralogous family members Hoxc8 and Hoxd8.
Trichotillomania is an “impulse-control disorder” in humans, characterised by repetitive stereotypical hair pulling from different areas
Barbering in mice can serve as an animal model of trichotillomania
Mice homozygous for a loss of function mutation in Hoxb8 gene (involved in grooming behaviour) display clinical signs of trichotillomania
Studies are needed to see if people with trichotillomania have the same mutation and whether prescription drugs that ameliorate trichotillomania can cut back grooming in Hoxb8 mice
We thank Judith A James for supplying the mice shown in the photograph and Yaser Dorri for his help with the photography. Contributors: Animal immunisation studies were carried out by BTK and RHS with TG's assistance. The manuscript was written by BTK and approved by RHS and TG.
Funding: This work was supported by NIH grant ARO1844 awarded to RHS and by funding from the Oklahoma Center for the Advancement of Science and Technology to RHS and BTK. Competing interests: None declared.
Ethical approval: The animal immunisation experiments described in the manuscript were approved by the Institutional Review Board.