Investigating the cellular basis of excessive grooming behavior in HoxB8 mutant mice

Excessive grooming behavior has been reported in Hoxb8 loss-of-function mutants. Since Hoxb8 expresses in various tissues in mice, the cause of the excessive grooming and hair removal phenotype was not clear. In this report we demonstrated that Hoxb8 is expressed in brain microglia hematopoietic systems. Immunological aberration in the function of hematopoietic system has been long considered as potential etiology for psychiatric disorders. Therefore bone marrow transplantation and conditional mutagenesis were conducted in our analysis to determine if malfunctioned hematopoietic system is associated with excessive grooming phenotype. Excessive grooming phenotype is rescued in hematopoietic chimeric Hoxb8 mutant mice carrying bone marrow cells derived from wildtype mice. On the other hand, nociception insensitivity remains evident in those phenotype rescued hematopoietic chimeras. Conditionally inactivation of Hoxb8 gene in hematopoietic systems recapitulated the hair removal and excessive grooming phenotype, but did not recapitulate dorsal spinal cord and sensory defects. These observations indicated that the sensory defects could be genetically separated from is not the primary cause the excessive grooming phenotype associated with the Hoxb8 disruption. Further, the histological test in skin shows no aberrant immune cell infiltration in the infected tissue. These observations support the conclusion that the hair loss and excessive grooming phenotype in Hoxb8 mutant mice is primary associated with the function of Hoxb8 in hematopoietic systems. This is also the first model systems to directly support the long existing hypothesis that dysfunctions of the hematopoietic system and immunological alterations can be lead to the etiology of behavioral disorders, such as obsessive compulsive disorder, major depression and schizophrenia.