Craniofacial anomalies in schizophrenia-relevant GFAP.HMOX10-12m mice

Abstract

Subtle craniofacial dysmorphology has been reported in schizophrenia patients. This dysmorphology includes midline facial elongation, frontonasal anomalies and a sexually dimorphic deviation from normal directional asymmetry of the face, with male patients showing reduced and female patients showing enhanced facial asymmetry relative to healthy control subjects. GFAP.HMOX1^0-12m transgenic mice (Mus musculus) that overexpress heme oxygenase-1 in astrocytes recapitulate many schizophrenia-relevant neurochemical, neuropathological and behavioral features. As morphogenesis of the brain, skull and face are highly interrelated, we hypothesized that GFAP.HMOX1^0-12m mice may exhibit craniofacial anomalies similar to those reported in persons with schizophrenia. We examined craniofacial anatomy in male GFAP.HMOX1^0-12m mice and wild-type control mice at the early adulthood age of 6-8 months. We used computer vision techniques for the extraction and analysis of mouse head shape parameters from systematically acquired 2D digital images, and confirmed our results with landmark-based geometric morphometrics. We performed skull bone morphometry using digital calipers to take linear distance measurements between known landmarks. Relative to controls, adult male GFAP.HMOX1^0-12m mice manifested craniofacial dysmorphology including elongation of the nasal bones, alteration of head shape anisotropy and reduction of directional asymmetry in facial shape features. These findings demonstrate that GFAP.HMOX1^0-12m mice exhibit craniofacial anomalies resembling those described in schizophrenia patients, implicating heme oxygenase-1 in their development. As a preclinical mouse model, GFAP.HMOX1^0-12m mice provide a novel opportunity for the study of the etiopathogenesis of craniofacial and other anomalies in schizophrenia and related disorders.

Keywords: animal model; craniofacial dysmorphology; facial asymmetry; heme oxygenase‐1; nasal bone; schizophrenia.