Craniofacial anomalies in schizophrenia‐relevant GFAP.HMOX1^0‐12m 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.