"CNS specific knock-outs for cre-lox"
Neurobiol at aol.com
Neurobiol at aol.com
Thu Sep 26 18:14:10 EST 1996
un691cs at genius.embnet.dkfz-heidelberg.de (z) started this subject by writing
>> here in the lab we would like to make CNS specific knock-outs
>> with the cre-lox system. For this, I am looking for a CNS (not
>> PNS !) specific promoter, which is either expressed only in CNS
>> neurons, or in CNS neurons as well as glia. neurofilament, 14-3-3,
>> vimentin, nestin or negrin won't do, as these are either
>> expressed in PNS neurons or outside by non-neural cells as well.
>Reply From: mhulsey at fcs.uga.edu (Martin G. Hulsey)
>Take a look at Retina-derived POU-domain factor-1 (J. Neurosci. 16(7):
>2261-2274;1996) or Na+/Cl(-)-dependent "orphan" transporter Rxt1 (J.
>Neurosci. Res. 42(3): 423-432; 1995.
>As an aside, do you think that CNS-relevant knockout models are >useful to
>learn about the role of gene products in normal animals (aside from a >role
>in neuronal development, perhaps)? The recent NPY knockout has me
>thinking otherwise, because the results were so discordant compared to
>I would submit that temporal control of cre or flp expression will prove
>to be as important as neuroanatomical control, if not more so. This is
>because it is now apparent that neural networks can develop in >alternative
>ways that can compensate for the total absence of an otherwise >important
>gene product like NPY.
First, I believe there was a report at the mouse meeting of a cre-lox
knockout made by crossing a cre transgene driven by the nestin promoter into
a strain that was knocked out for something (I forget what ) that is lethal
in embryogenesis when homozygous. I've been too lazy to look up the
expression pattern of nestin, but I gather from your comments that the PNS
should have been affected, too. Does anyone have a better knowledge of this
work? I wasn't at the meeting and heard it secondhand...
Second, Martin, I agree with you that it is very nice but not sufficient to
restrict the knockout to a particular cell type by breeding to a tissue
specific promoter-cre mouse line. I have a couple of reservations. The
first is practical. Not a lot of promoters are really tissue specific, and
it doesn't take much cre expression to irrevokably alter a cell that might be
the first in a lineage of any organ. I suspect there will be a few
undiagnosed chimeras caused by this method if people don't look at the
animals thoroughly. The second reason I think that the cre needs to be
delivered temporally is of course the issue you bring up- that delivery of a
knockout to a specific cell type- by retrovirus? naked DNA? liposomes?- is
the next step, AFTER the simple knockout is replaced with the
Interesting stuff. I'd like to continue this discussion. Anyone else?
jloring at mdyn.com
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