Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2004;11(5-6):221-31.
doi: 10.3727/000000003783992234.

Mouse Huntington's disease homolog mRNA levels: variation and allele effects

Karen T Dixon  1 , Jamie A Cearley, Jesse M Hunter, Peter J Detloff
Affiliations

Mouse Huntington's disease homolog mRNA levels: variation and allele effects

Karen T Dixon et al. Gene Expr. 2004.

Abstract

Huntington's disease homolog (Hdh) mRNA levels in mice with different Hdh alleles were measured. Brain Hdh mRNA levels varied up to threefold in genetically identical wild-type mice, indicating nongenetic factors influence Hdh expression. Striatal Hdh mRNA levels from an allele with a repeat expanded to 150 CAGs were diminished compared with wild-type and showed variation that might contribute to phenotypic variability in the Hdh(CAG)150 knock-in mouse model. To determine whether Hdh mRNA levels are tightly regulated, we assessed these levels in mice heterozygous for a deletion of the Hdh promoter. The loss of one allele reduced Hdh mRNA levels in most tissues, suggesting mechanisms to maintain Hdh mRNA levels are not in effect and should not impede therapies designed to destroy mutant huntingtin mRNA. Finally, we found a correlation between tissue mRNA levels and the susceptibility of the Hdh locus to Cre-mediated deletion. The two tissues with the highest levels of Hdh mRNA, testes and brain, were the only tissues susceptible to Cre-mediated recombination between loxP sites at Hdh locus. In contrast, the same Cre-expressing line caused recombination in every tissue for loxP sites at another genomic location. The pattern of Cre susceptibility at Hdh suggests a correlation between chromatin accessibility and high levels of Hdh expression in testes and brain.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Variation in brain Hdh mRNA levels in 11 C57BL/6 mice. Top: Bars show the level of Hdh mRNA relative to the maximum (mouse #1 = 100%). The ID number of each mouse is shown below each bar. Error bars represent the SEM (n = 15 replicates per mouse). Bottom: Statistical comparison of Hdh mRNA levels from each mouse is represented by horizontal bars. Shaded areas within each bar indicate that a statistically significant difference was found for brain Hdh mRNA levels between mouse ID on left and mouse ID above (Kruskal-Wallis with Dunn’s post test, *p < 0.05, **p < 0.01, ***p < 0.001).
Figure 2
Figure 2
Variation in striatal Hdh mRNA levels. Top: Striatal Hdh mRNA levels relative to maximum wild-type mouse are shown for 10 wild-type (black bars) and 12 homozygous Hdh (CAG)150 mice (gray bars). Each wild-type mouse was assigned a number 1–10 and each mutant a number 1–12 (these numbers do not correspond to mouse numbers in Fig. 1). Error bars show the SEM. Bottom: Statistical comparison of Hdh mRNA levels from each mouse is represented by horizontal bars. Shaded areas within each bar indicate that a statistically significant difference was found for brain Hdh mRNA levels between mouse ID next to bar [left for wild-type mice, right for homozygous Hdh (CAG)150 mice] and mouse ID above (Kruskal-Wallis with Dunn’s post test, *p < 0.05, **p < 0.01, ***p < 0.001).
Figure 3
Figure 3
Mean and variation of relative Hdh mRNA levels in different tissues. (A) Black bars indicate mean level of Hdh mRNA for six wild-type mice (Hdh+/+) in eight different tissues relative to wild-type testes (maximum). Open bars indicate mean level of Hdh mRNA for six heterozygous promoter deletion mice (Hdh+/-) for each tissue relative to wild-type testes (maximum). T, testes; B, brain; K, kidney; S, spleen; H, heart; L, liver; P, pancreas; M, skeletal muscle. The error bars represent SD for the 4–6 measurements taken on each of six mice represented by the vertical bar (includes mouse-to-mouse and experimental variation). The entire figure represents 540 measurements of Hdh mRNA levels. Statistical comparison of Hdh+/+ and Hdh+/- mice for each tissue by the Mann-Whitney test yielded p values shown above bars (NS, not significantly different or p > 0.05). (B) Statistical comparison of Hdh mRNA levels from each tissue in Hdh+/+ mice is represented by horizontal bars. Shaded areas within each bar indicate that a statistically significant difference was found for Hdh mRNA levels between tissue on left and tissue label above bar (Kruskal-Wallis with Dunn’s post test, *p < 0.05, **p < 0.01, ***p < 0.001). (C) Same as (B), but for tissues in Hdh+/− mice.
Figure 4
Figure 4
Hdh mRNA tissue levels in individual mice. Top: Bars represent Hdh mRNA level from one tissue of a single wild-type mouse as a percentage of the maximum (testes of wild-type mouse ID #2). Mouse ID numbers correspond to those in Figure 1. Error bars represent the SEM as calculated from 4–8 replicates on each tissue. Letters represent different tissues as described in the legend for Figure 3. These data are a different representation of the averaged data from Figure 3. Bottom: Same as top panel except bars indicate Hdh mRNA levels for tissues in Hdh+/− mice as a percentage of maximum (testes of wild-type mouse ID #2).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ambrose C. M.; Duyao M. P.; Barnes G.; Bates G. P.; Lin C. S.; et al. Structure and expression of the Huntington’s disease gene: Evidence against simple in-activation due to an expanded CAG repeat. Somat. Cell Mol. Genet. 20:27–38; 1994. - PubMed
    1. Andrew S. E.; Goldberg Y. P.; Kremer B.; Telenius H.; Theilmann J.; et al. The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington’s disease. Nat. Genet. 4:398–403; 1993. - PubMed
    1. Barnes G. T.; Duyao M. P.; Ambrose C. M.; McNeil S.; Persichetti F.; et al. Mouse Huntington’s disease gene homolog (Hdh). Somat. Cell Mol. Genet. 20:87–97; 1994. - PubMed
    1. Bhide P. G.; Day M.; Sapp E.; Schwarz C.; Sheth A.; et al. Expression of normal and mutant huntingtin in the developing brain. J. Neurosci. 16:5523–5535; 1996. - PMC - PubMed
    1. Blake W.; Kaern M.; Cantor C.; Collins J. Noise in eukaryotic gene expression. Nature 422:633–637; 2003. - PubMed

Publication types

MeSH terms

LinkOut - more resources