Brainbow mice: A technicolor approach to map the neuronal circuits
Fluorescent protein transgenic mice
Understanding how the precise interconnections of neurons account for brain functions has been a preoccupation of neuroscientists for over a century. The primary obstacle that researchers have faced when attempting to map the neural circuitry of the brain has been their inability to clearly resolve the cellular elements involved. Scientists have tried a number of approaches, from simple histological stains (developed generations ago) that allow them to distinguish small subsets of neurons to sophisticated array tomography (Micheva and Smith 2007). Still, so far it has been difficult to develop a comprehensive, precise view of the brain's wiring diagram.
Innovations and Advantages
This invention is a set of fluorescent protein transgenic mice whose neurons have the potential to display every color of the rainbow. In these mice, various neuronal cell types possess multiple fluorescent protein sequences uniquely flanked with pairs of incompatible Lox sites alternated to create mutually exclusive recombination events. Each neuron may express one of a wide variety of possible fluorescent protein combinations, and therefore emit a distinctive hue. Depending on the type of analysis used, over 89-166 colors may be distinguished. This, in turn, allows the unambiguous identification and tracing of multiple cells within a neuron ensemble, a critical step toward mapping the ''connectome''. Such wiring diagrams should lead to better understanding of diseases such as autism and schizophrenia, as well as new insight into learning and other cognitive functions.
Brainbow mice are available through Jackson Laboratory. Use of Brainbow mice by companies or for-profit entities requires a separate commercial license from Harvard University.
JAX 007901 (line H)
Cells labeled: peripheral and central neurons, including peripheral sensory neurons, cranial and spinal motor neurons (~75%), retinal ganglion cells, dentate gyrus granule cells, pyramidal neurons of CA1 and some cortical areas, and inferior olive neurons and associated mossy fibers (~20%).
JAX 007910 (line L)
Cells labeled: same as line H, but also a few cerebellar Purkinje neurons.
JAX 007911 (line M)
Cells labeled: astrocytes of all areas of the brain and spinal cord, dentate gyrus granule cells, and limited expression in a few scattered neurons.
JAX 007921 (line R)
Cells labeled: same as line H, but also a few cerebellar Purkinje cells. However, expression is observed in the nucleus of all cells.
-Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. 2007. Nature 450:56-52.
-A technicolour approach to the connectome. 2008. Nature Reviews Neuroscience 9:417-22.
Lichtman, Jeffrey W.
Sanes, Joshua R.
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Reference Harvard Case #2611