Visualization of the Dynamics of Gene Expression in the Living Mouse

Ryan, Amy; Scrable, Heidi

doi:10.1162/15353500200403193

Cited by 9 publications

(5 citation statements)

References 18 publications

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“…In a subsequent study, similar control of gene expression during embryogenesis was demonstrated in vivo for a luciferase reporter gene under the control of the ubiquitous Huntingtin promoter with introduced LacO sites (Huntingtin Lac O ‐luciferase) (Ryan & Scrable, 2004). In this study it was shown that luciferase activity could be regulated in live offspring in utero by the addition of IPTG to the drinking water of the pregnant dam (Ryan & Scrable, 2004).…”

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confidence: 76%

Genetically manipulated mice: a powerful tool with unsuspected caveats

Matthaei

2007

The Journal of Physiology

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Although genetic manipulations in mice have provided a powerful tool for investigating gene function in vivo, recent studies have uncovered a number of developmental phenomena that complicate the attribution of phenotype to the specific genetic change. A more realistic approach has been to modulate gene expression and function in a temporal and tissue-specific manner. The most common of these methods, the CreLoxP and tetracycline response systems, are surveyed here and their recently identified shortcomings discussed, along with a less well known system based on the E. coli lac operon and modified for use in mammals. The potential for further complications in interpretation due to hitherto unexpected epigenetic effects involving transfer of RNA or protein in oocytes or sperm is also explored. Given these problems we reiterate the necessity for the use of completely reversible methods that will allow each experimental group of animals to act as their own control. Using these methods with a number of specific modifications to eliminate non-specific effects from random insertion sites and inducer molecules, the full potential of genetic manipulation studies should be realized.

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confidence: 76%

Genetically manipulated mice: a powerful tool with unsuspected caveats

Matthaei

2007

The Journal of Physiology

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“…Orientation was verified by analytical restriction enzyme digest. The generation of the human pHDluc reporter construct has been described previously (Ryan and Scrable, 2004).…”

Section: Generation Of Huntingtin Reporter Constructsmentioning

confidence: 99%

Genetic interaction between expanded murine Hdh alleles and p53 reveal deleterious effects of p53 on Huntington's disease pathogenesis

Ryan

Zeitlin

Scrable

2006

Neurobiology of Disease

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Huntingtin, the protein product of the Huntington's disease (HD) gene is known to interact with the tumor suppressor p53. It has recently been shown that activation of p53 upregulates the level of huntingtin, both in vitro and in vivo, while p53 deficiency in HD-transgenic flies and mice has been found to be beneficial. To explore further the involvement of p53 in HD pathogenesis, we generated mice homozygous for a mutant allele of Hdh (Hdh Q140 ) and with zero, one, or two functional alleles of p53. p53 deficiency resulted in a reduction of mutant huntingtin expression in brain and testis, an increase in proenkephalin mRNA expression, and a significant increase in nuclear aggregate formation in the striatum. Because aggregation of mutant huntingtin is suggested to be a protective mechanism, both the increase in aggregate load and the restoration of proenkephalin expression suggest a functional rescue of HD phenotypes by p53 deficiency.

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“…For instance, a tetO and lacO doubly modified gene could be controlled in two different tissues using specific combinations of lacI and (r)tTA or (r)tTS under the control of two tissuespecific promoters; addition or removal of doxycycline and IPTG would then determine the specific activation status in each of the tissues in a reversible fashion. A transgenic model using this system and a luciferase reporter that allows the evaluation of the dynamics of gene expression in the living animal has recently been described (72).…”

Section: The Lac Systemmentioning

confidence: 99%

Controlled gene activation and inactivation in the mouse

Mallo

2006

Front Biosci

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The emergence of techniques that allow fine manipulation of gene expression in the mouse have changed the way biomedically relevant processes are studied, as they allow their analysis in the living animal. In addition, this has opened the possibility to generate animal models for several human diseases, which are useful both for understanding the disease' s physiopathological mechanisms and for the eventual evaluation of novel therapeutic approaches. Many of the gene manipulation systems currently employed in the mouse are based on regulatory mechanisms normally operating in yeast and prokaryotic organisms. This has allowed specific experimental control with very limited unspecific interference with the normal physiology of the cell. Some of these systems use elements that permit transcriptional regulation of a particular gene or genes. Among them, I will discuss in detail the tet, lac and Gal4/UAS systems, which are among the most popular of these transcriptional systems because they can be used to achieve spatial and temporal control on the expression of a specific gene in a reversible fashion. The other major group of systems currently employed to manipulate gene expression in the mouse is based on site-specific recombination reactions. The Cre/lox and FLP/FRT systems are the most popular of these. I will discuss how these recombination systems are used in the mouse with special focus on their use to achieve specific gene activation.

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Visualization of the Dynamics of Gene Expression in the Living Mouse

Cited by 9 publications

References 18 publications

Genetically manipulated mice: a powerful tool with unsuspected caveats

Genetically manipulated mice: a powerful tool with unsuspected caveats

Genetic interaction between expanded murine Hdh alleles and p53 reveal deleterious effects of p53 on Huntington's disease pathogenesis

Controlled gene activation and inactivation in the mouse

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