Novel Dixdc1 Mouse Line for Study of Major Psychiatric Disorders and Cancer

Background

The Dixdc1 protein may play an important role in the pathogenesis of schizophrenia, major depressive disorder, bipolar disorder, autism and other major psychiatric disorders.  In addition, Dixdc1 may also contribute to cancer metastasis, invasiveness and planar cell polarity.  Molecular signaling pathways potentially involving Dixdc1 include the Wnt/b-catenin, Nde1/CDK5 and the TGF-b pathways.  Importantly, Dixdc1 protein is an establised partner of the Disc1 protein, the product of one of the best-established neuropsychiatric susceptibility genes (DISC1).  Previous studies have utilized RNA interference to knock down Dixdc1 protein.  However, a genetic knockout in mice, an important rsearch tool that would be very useful for studying Dixdc1 function in disease, has not been described in the scientific literature to date.

Technology Description

UCSF investigators have generated a Dixdc1 knockout mouse line by making a targeted mutation in the genetic locus corresponding to Dixdc1, a conserved homolog of the DIXDC1 gene found in homo sapiens and other vertebrates.  This mutation was designed such that the essential exons B2, 2 and 3 of the gene were replaced by a piece of foreign DNA encoding the neomycin-resistance gene, which is predicted to render the allele non-functional by disrupting the translation of all characterized Dixdc1 transcripts.  ES cells carrying this mutation were made by homologous recombination, and a mouse line derived from the correctly targeted ES cells was created using embryo manipulation techniques (Translational Psychiatry 2011 3(2):162-174).  This invention is a valuable model that enables study of the roles of Dixdc1 gene and its RNA and protein products during development and postnatally.

Applications

• Study Dixdc1's role in the pathogenesis of major psychiatric disorders, including schizophrenia, major depressive disorder, bipolar disorder and autism
• Study Dixdc1's role in cancer etiology, pathogenesis, metastasis and invasiveness
• Study Dixdc1's role in planar cell polarity pathways involved in wound healing and stem cell biology

Related Materials

• Kivimae S et al. (2011). Abnormal behavior in mice mutant for the Disc1 binding partner, Dixdc1. 3(2):162-74. - 09/27/2011