Generation of a new Slc20a2 knockout mouse line as in vivo model for primary brain calcification.

Primary brain calcification (PBC) is a neurodegenerative disease that causes bilateral ectopic calcification in the brain. In this study, using newly generated Slc20a2 knockout (Slc20a2^-/-) mice, we establish an in vivo model for PBC. In contrast to heterozygous Slc20a2^+/- mice (9/9 animals) showing no obvious abnormalities, the homozygous Slc20a2^-/- mice exhibited severe calcification at 11 months of age (5/5 animals). Whilst smaller in size and number, the deposits were also detectable in 5-month-old Slc20a2^-/- mice (2/2 animals). By contrast, no obvious alterations were detectable in visceral organs, including the lung, kidney, liver, and spleen. Consistently, in PBC patients, despite the systemic mineral metabolic disturbance, calcification occurs only in a brain restricted manner. Hence, these observations suggest that our mouse model is capable of recapitulating certain aspects of human PBC etiology. In summary, our data suggested the utility of an in vivo PBC mouse model in understanding the pathological mechanisms behind brain calcification, which leads in development of novel therapeutics against PBC.