The normal neonatal canine brain exhibits marked differences from that of the mature brain. With development into adulthood there is a decrease in relative water content and progressive myelination; these changes are observable with magnetic resonance (MR) imaging and are characterized by a repeatable and predictable time course. We characterized these developmental changes on common MR imaging sequences and identified clinically useful milestones of transition. To accomplish this, 17 normal dogs underwent MR imaging of the brain at various times after birth from 1 to 36 weeks. Sequences acquired were T1-weighted, T2-weighted, Fluid Attenuated Inversion Recovery, Short Tau Inversion Recovery and Diffusion Weighted Imaging sequences. The images were assessed subjectively for gray and white matter relative signal intensity and results correlated with histologic findings. The development of the neonatal canine brain follows a pattern that qualitatively matches that observed in humans, and which can be characterized adequately on T1-weighted and T2-weighted images. At birth, the relative gray matter to white matter signal intensity of the cortex is reversed from that of the adult with an isointense transition at 3–4 weeks on T1-weighted and 4–8 weeks on T2-weighted images. This is followed by the expected mature gray matter to white matter relative intensity that undergoes continued development to a mostly adult appearance by 16 weeks. On the Fluid Attenuated Inversion Recovery sequence the cortical gray and white matter exhibit an additional signal intensity reversal during the juvenile period that is due to the initial high relative water content at the subcortical white matter, with its marked T1 relaxation effect.

Valosin Containing Protein (VCP) disease is an autosomal dominant disorder caused by mutations in the VCP gene and is associated with progressive muscle weakness and atrophy. Affected individuals exhibit striking scapular winging due to shoulder girdle weakness. Currently, there are no treatments available and patients are dying early from cardiac and respiratory failure, typically in their 40's and 50's. The generation of disease-specific induced pluripotent stem cells (iPSC) offers a novel platform to investigate mechanisms of VCP disease and potential treatments similar to other disease models including Amyotrophic Lateral Sclerosis (ALS), Duchenne muscular dystrophy (DMD), Parkinson's disease (PD), Alzheimer's disease (AD), Best Disease (BD), and type I juvenile diabetes mellitus (T1DM). Herein, we report the generation and characterization of a human iPSC line to examine the cellular and molecular processes underlying VCP disease. The VCP iPSC line expressed specific pluripotency markers NANOG, SSEA4, OCT-4, TRA-1-81 and exhibited characteristic morphology. We differentiated the human iPSC cell line into a neuronal lineage confirmed by TUJ-1 staining, a neuronal class III β-tubulin marker. We detected higher protein expression levels of ubiquitin (Ub), TAR DNA-binding protein-43 (TDP-43), Light Chain 3-I/II (LC3), p62/SQSTM1, and optineurin (OPN) in the iPSC neural lineage compared to the control neural line. Collectively, our results demonstrate that patient-specific iPSC technology may provide useful disease modeling for understanding the complex mechanisms and for developing novel treatments of VCP and related disorders.

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