Timothy Syndrome (TS) arises from a point mutation in the human voltage-gated L-type Ca2+ channel (Cav1.2). TS is associated with cardiac arrhythmias and sudden cardiac death, as well as congenital heart disease, impaired cognitive function, and autism spectrum disorders. TS results from a de novo gain-of-function mutation which affects the voltage dependent component of Cav1.2 inactivation. We created a knock-in TS mouse. No homozygous TS mice survived, but heterozygous TS2-NEO mice (with the mutation and the neocassette in situ) had a normal outward appearance and survived to reproductive age. Previously, we have demonstrated that these mice exhibit the triad of Autistic traits. In this paper we document other aspects of these mice including Cav1.2 isoform expression levels, normal physical strength, brain anatomy and a marked propensity towards self-injurious scratching. Gross brain anatomy was not markedly different in TS2-NEO mice compared to control littermates, and no missing structures were noted. The lack of obvious changes in brain structure is consistent with theTS2-NEO mice may provide a significant tool in understanding the role of calcium channel inactivation in both cardiac function and brain development.
Pathologists routinely interpret gross and microscopic specimens to render diagnoses and to engage in a broad spectrum of investigative research. Multiple studies have demonstrated that imaging technologies have progressed to a level at which properly digitized specimens provide sufficient quality comparable to the traditional glass slides examinations. Continued advancements in this area will have a profound impact on the manner in which pathology is conducted from this point on. Several leading institutions have already undertaken ambitious projects directed toward digitally imaging, archiving, and sharing pathology specimens. As a result of these advances, the use of informatics in diagnostic and investigative pathology applications is expanding rapidly. In addition, the advent of novel technologies such as multispectral imaging makes it possible to visualize and analyze imaged specimens using multiple wavelengths simultaneously. As these powerful technologies become increasingly accepted and adopted, the opportunities for gaining new insight into the underlying mechanisms of diseases as well as the potential for discriminating among subtypes of pathologies are growing accordingly.
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