Watching the Energy Flow in Neurons: Jackson Laboratory Scientist Helps Develop Two Fluorescent Mouse Strains
JAX® NOTES Issue 507, Fall 2007
One of our scientists, Robert Burgess PhD, recently helped construct and import two transgenic strains with fluorescently-labeled neuronal mitochondria into The Jackson Laboratory (Misgeld et al. 2007). The two strains, STOCK Tg(Thy1-CFP/COX8A)C1Lich/J (006614) and STOCK Tg(Thy1-CFP/COX8)S2Lich/J (006617), dubbed "MitoMice," should be particularly useful for determining the role of neuronal mitochondria in the pathophysiology of neuromuscular diseases such as amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's disease.
Shedding Light on Neuronal Functions
Selectively labeling neurons with green fluorescent protein (GFP) or its spectral variants, such as cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP), has made studying neuronal structure, development, and function in mammals considerably easier (Feng et al. 2000; Walsh and Lichtman 2003). One of the features of fluorescently-labeled neurons is that their normal functions and activities can be examined in vivo through fluorescent microscopy (Fig. 1). Subsets of neurons and their components can also be labeled, allowing researchers to characterize the complex organization of the central nervous system.
How MitoMice Shine
MitoMice are unique because the mitochondria in their motor neurons have been fluorescently labeled. Some motor neurons are exceptionally long, approximately a meter long from their cell bodies in the spinal cord to their nerve endings, where they connect to and effect the contraction of muscle fibers. Disrupted transport of motor neuronal mitochondria has been implicated in a variety of neurological diseases, including ALS. MitoMice could be used in combination with ALS mouse model B6.Cg-Tg(SOD1*G93A)1Gur/J (004435) to study how the disease progresses in vivo (Frietman 2007).
To selectively label the neuronal mitochondria in MitoMice, the researchers used well-established neuronal promoters, Thy-1 and Eno2 (Nse), to drive the expression of CFP or YFP fused to a mitochondrial targeting sequence from the human cytochrome c oxidase subunit 8A gene.
Obtaining MitoMice
We are in the process of making the two MitoMice strains available to the global scientific community. You may register interest in these strains at their respective strain data sheets in the JAX® Mice Database, www.jax.org/jaxmice. Simply search the database by using the strain stock numbers listed earlier.
We distribute over 100 other fluorescently labeled JAX® Mice strains that can be used to monitor a variety of physiological and biochemical processes in vivo. For information about these strains, please visit the Web page for Research Tools: Fluorescent Protein strains, or contact JAX® technical information services at 800-422-6423, 207-288-5845, or micetech@jax.org.
References
(Author in bold is a Jackson Laboratory scientist.)
Feng G, Mellor RH, Bernstein M, Keller-Peck C, Nguyen QT, Wallace M, Nerbonne JM, Lichtman JW, Sanes JR. 2000. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28:41-51.
Frietman R. 2007. Mice show how mitochondria flow in nerve cells. Amyotrophic Lateral Sclerosis Association Web site. June 4 2007 press release.
Walsh MK, Lichtman JW. 2003. In vivo time-lapse imaging of synaptic takeover associated with naturally occurring synapse elimination. Neuron 37:67-73.
Misgeld T, Kerschensteiner M, Bareyre FM, Burgess RW, Lichtman JW. 2007. Imaging axonal transport of mitochondria in vivo. Nat Methods 4:559-61.
