gene regulation in knockout mice

[Peter Ashby]

In article <8578bd43.0210312031.3befd98f at posting.google.com>,
 imperat at hotmail.com (Don Incognito) wrote:

> yongwee at hotmail.com ("Yong Wee Wong") wrote in message 
> > I am working on the gene differential expression screening (by microarray) 
> > using a gene deficient mouse model. In the array screening, there is a gene 
> > 3 folds down-regulated. This gene is very closed to the knockout gene on 
> > the 
> > same chromosome(About 1 000 000bp apart). Has anybody come across this case 
> > before in the knockout model? Could this downregulation caused by physical 
> > location on the chromosome/ or the transgene? thanks
> 
> I imagine it would be more parsimonious to think that the gene you
> knocked out directly or indirectly influences expression of the
> downregulated gene, not so?

Not without a lot more evidence than this, no. There have been a number 
of reports of Neo genes in knockouts affecting genes transcriptionally 
downstream of the neo gene. For a review see: 
E. N. Olson, H.-H. Arnold, P. W. J. Rigby, and B. J. Wold
Know Your Neighbors: Three Phenotypes in Null Mutants of the Myogenic 
bHLH Gene MRF4  Cell 1996 85: 1.

If the knockout gene still contains the neo it would be more 
parsimonious to blame that in the absence of other factors.

Another alternative is the removal or disruption of a long range 
regulatory element for the second gene within the introns of the first 
as in:
 Lettice LA, Horikoshi T, Heaney SJ, van Baren MJ, van der Linde HC, 
Breedveld GJ, Joosse M, Akarsu N, Oostra BA, Endo N, Shibata M, Suzuki 
M, Takahashi E, Shinka T, Nakahori Y, Ayusawa D, Nakabayashi K, Scherer 
SW, Heutink P, Hill RE, Noji S. Related Articles, Links
    Disruption of a long-range cis-acting regulator for Shh causes 
preaxial polydactyly.
    Proc Natl Acad Sci U S A. 2002 May 28;99(11):7548-53.
PMID: 12032320

Peter

-- 
Peter Ashby
Wellcome Trust Biocentre
University of Dundee, Scotland
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