RESUMO
The loss of motor neurons (MNs) is a hallmark of the neuromuscular disease spinal muscular atrophy (SMA); however, it is unclear whether this phenotype autonomously originates within the MN. To address this question, we developed an inducible mouse model of severe SMA that has perinatal lethality, decreased motor function, motor unit pathology, and hyperexcitable MNs. Using an Hb9-Cre allele, we increased Smn levels autonomously within MNs and demonstrate that MN rescue significantly improves all phenotypes and pathologies commonly described in SMA mice. MN rescue also corrects hyperexcitability in SMA motor neurons and prevents sensory-motor synaptic stripping. Survival in MN-rescued SMA mice is extended by only 5 d, due in part to failed autonomic innervation of the heart. Collectively, this work demonstrates that the SMA phenotype autonomously originates in MNs and that sensory-motor synapse loss is a consequence, not a cause, of MN dysfunction.
Assuntos
Neurônios Motores/patologia , Atrofia Muscular Espinal/patologia , Células Receptoras Sensoriais/patologia , Animais , Animais Recém-Nascidos , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Neurônios Motores/fisiologia , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/fisiopatologia , Junção Neuromuscular/patologia , Junção Neuromuscular/fisiologia , Células Receptoras Sensoriais/fisiologiaRESUMO
BACKGROUND: To determine whether introducing clinical skills during the second year of medical school, via a competency-based College system approach, improves comfort level for medical students entering third-year clinical rotations. METHOD: From 2003-2005, two cohorts of third-year medical students at the University of Washington were surveyed on their comfort level in the categories of history taking, physical examination, communication, and patient care. RESULTS: The cohort of students exposed to the College system reported a statistically significant greater comfort level in half of the measured areas, and in at least one area within each general category. No area of study showed a statistically significant decline. CONCLUSION: A competency-based College system improves medical student comfort in core clinical skills at the start of the third year curriculum.