RESUMEN
BACKGROUND: A two-year longitudinal study composed of morphometric MRI measures and cognitive behavioral evaluation was performed on a transgenic Huntington's disease (HD) monkey. rHD1, a transgenic HD monkey expressing exon 1 of the human gene encoding huntingtin (HTT) with 29 CAG repeats regulated by a human polyubiquitin C promoter was used together with four age-matched wild-type control monkeys. This is the first study on a primate model of human HD based on longitudinal clinical measurements. RESULTS: Changes in striatal and hippocampal volumes in rHD1 were observed with progressive impairment in motor functions and cognitive decline, including deficits in learning stimulus-reward associations, recognition memory and spatial memory. The results demonstrate a progressive cognitive decline and morphometric changes in the striatum and hippocampus in a transgenic HD monkey. CONCLUSIONS: This is the first study on a primate model of human HD based on longitudinal clinical measurements. While this study is based a single HD monkey, an ongoing longitudinal study with additional HD monkeys will be important for the confirmation of our findings. A nonhuman primate model of HD could complement other animal models of HD to better understand the pathogenesis of HD and future development of diagnostics and therapeutics through longitudinal assessment.
Asunto(s)
Encéfalo/metabolismo , Encéfalo/patología , Modelos Animales de Enfermedad , Enfermedad de Huntington/genética , Enfermedad de Huntington/patología , Proteínas del Tejido Nervioso/genética , Envejecimiento/genética , Envejecimiento/patología , Animales , Animales Modificados Genéticamente , Humanos , Proteína Huntingtina , Estudios Longitudinales , Macaca mulatta , Masculino , Tamaño de los Órganos/genética , Distribución TisularRESUMEN
Crossed fused renal ectopia and the presence of a supernumerary kidney are both rare congenital variants that are often asymptomatic but may be associated with other developmental anomalies. Here we present a case of a 20-year-old male with a known diagnosis of crossed fused renal ectopia as well as a history of imperforate anus and tethered spinal cord treated in infancy. He presented to the emergency room with symptoms of flank pain, and a noncontrast computed tomography (CT) scan revealed a 4-mm stone in the distal left ureter. CT scan also revealed that the patient's right kidney was not crossed and fused to the left kidney as previously believed, but rather it was crossed and fused to a supernumerary kidney abutting the inferomedial aspect of an orthotopic left kidney. This is a unique example of two rare coexisting renal anomalies not previously detected on a nuclear medicine renal scan and serial renal ultrasounds obtained earlier in the the patient's life.
RESUMEN
One of the roadblocks to developing effective therapeutics for Huntington disease (HD) is the lack of animal models that develop progressive clinical traits comparable to those seen in patients. Here we report a longitudinal study that encompasses cognitive and motor assessment, and neuroimaging of a group of transgenic HD and control monkeys from infancy to adulthood. Along with progressive cognitive and motor impairment, neuroimaging revealed a progressive reduction in striatal volume. Magnetic resonance spectroscopy at 48 months of age revealed a decrease of N-acetylaspartate (NAA), further suggesting neuronal damage/loss in the striatum. Postmortem neuropathological analyses revealed significant neuronal loss in the striatum. Our results indicate that HD monkeys share similar disease patterns with HD patients, making them potentially suitable as a preclinical HD animal model.