Characterization of the Von Willebrand Domain-Containing Protein 8 (Vwa8) Gene in Mouse

The Drosophila gene c12.2 was isolated in a screen examining mRNA binding proteins. Drosophila c12.2 is the mouse Vwa8 homolog. Various genome-wide associated studies have linked human Vwa8 to both neurological and oncological pathologies, which include autism, bipolar disorder, comorbid migraine, and acute myeloid leukemia, however, the function and role of the VWA8 protein remain poorly understood. To further analyze the Vwa8 gene in mouse, gene structure, protein homology modeling, and gene expression patterns were examined throughout mouse development. Our analyses indicate that the mouse Vwa8 gene produces two transcripts; the full-length Vwa8a is highly expressed relative to the truncated Vwa8b transcript across all developmental time points and tissues analyzed. Protein homology modeling indicates that VWA8a belongs to a novel protein superfamily containing both the midasin and cytoplasmic dynein 1 heavy chain 1 proteins. These data establish the development timeline and expression profile for both Vwa8a and Vwa8b, paving the way for future studies to determine the cellular role(s) of this highly conserved protein family. Additionally, a new scientific reagent, the conditional-ready Vwa8 tm1c knockout mouse was generated. This novel reagent provides the ability of tissue specific Vwa8 knockout by mating the Vwa8 tm1c mouse with a Cre-recombinase expressing mouse. Future work aims at analyzing the VWA8 protein in mouse to determine its function(s) in a mammalian system.