Expression of a foreign gene in a line of transgenic mice is modulated by a chromosomal position effect

1990 ◽  
Vol 10 (3) ◽  
pp. 1192-1198
Author(s):  
R al-Shawi ◽  
J Kinnaird ◽  
J Burke ◽  
J O Bishop
Keyword(s):  
Transgenic Mice ◽  
Position Effect ◽  
Insertion Site ◽  
Foreign Gene ◽  
Aberrant Expression ◽  
Transgenic Mouse Line ◽  
Chromosomal Position ◽  
Multiple Copies ◽  
Chromosomal Position Effect ◽  
Or Gene

Unusual aberrant expression of a foreign gene in a particular transgenic mouse line is often attributed to chromosomal position effect, although proof of this is lacking. An alternative explanation is that expression has been modified by the arrangement of multiple copies of the foreign gene at the insertion site or by mutation or gene rearrangement. We have distinguished between these explanations in the case of one particular transgenic line by recovering the aberrantly expressed foreign DNA and reintroducing it into the mouse genome to produce secondary transgenic mice. The expression pattern of the gene in the secondary transgenic mice was normal, showing that this case of aberrant expression is due to a chromosomal position effect.

scholarly journals Expression of a foreign gene in a line of transgenic mice is modulated by a chromosomal position effect.

1990 ◽  
Vol 10 (3) ◽  
pp. 1192-1198 ◽  
Author(s):  
R al-Shawi ◽  
J Kinnaird ◽  
J Burke ◽  
J O Bishop
Keyword(s):  
Transgenic Mice ◽  
Position Effect ◽  
Insertion Site ◽  
Foreign Gene ◽  
Aberrant Expression ◽  
Transgenic Mouse Line ◽  
Chromosomal Position ◽  
Multiple Copies ◽  
Chromosomal Position Effect ◽  
Or Gene

Unusual aberrant expression of a foreign gene in a particular transgenic mouse line is often attributed to chromosomal position effect, although proof of this is lacking. An alternative explanation is that expression has been modified by the arrangement of multiple copies of the foreign gene at the insertion site or by mutation or gene rearrangement. We have distinguished between these explanations in the case of one particular transgenic line by recovering the aberrantly expressed foreign DNA and reintroducing it into the mouse genome to produce secondary transgenic mice. The expression pattern of the gene in the secondary transgenic mice was normal, showing that this case of aberrant expression is due to a chromosomal position effect.

α-Thalassemia resulting from a negative chromosomal position effect

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 800-807
Author(s):  
Virginia M. Barbour ◽  
Cristina Tufarelli ◽  
Jacqueline A. Sharpe ◽  
Zoe E. Smith ◽  
Helena Ayyub ◽  
...  
Keyword(s):  
Cpg Island ◽  
Regulatory Element ◽  
Globin Gene ◽  
Position Effect ◽  
Single Family ◽  
Structural Genes ◽  
Chromosomal Position ◽  
Chromosomal Position Effect ◽  
Globin Promoter ◽  
Globin Gene Expression

To date, all of the chromosomal deletions that cause -thalassemia remove the structural  genes and/or their regulatory element (HS –40). A unique deletion occurs in a single family that juxtaposes a region that normally lies approximately 18-kilobase downstream of the human  cluster, next to a structurally normal -globin gene, and silences its expression. During development, the CpG island associated with the -globin promoter in the rearranged chromosome becomes densely methylated and insensitive to endonucleases, demonstrating that the normal chromatin structure around the -globin gene is perturbed by this mutation and that the gene is inactivated by a negative chromosomal position effect. These findings highlight the importance of the chromosomal environment in regulating globin gene expression.

α-Thalassemia resulting from a negative chromosomal position effect

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 800-807 ◽  
Author(s):  
Virginia M. Barbour ◽  
Cristina Tufarelli ◽  
Jacqueline A. Sharpe ◽  
Zoe E. Smith ◽  
Helena Ayyub ◽  
...  
Keyword(s):  
Cpg Island ◽  
Regulatory Element ◽  
Globin Gene ◽  
Position Effect ◽  
Single Family ◽  
Structural Genes ◽  
Chromosomal Position ◽  
Chromosomal Position Effect ◽  
Globin Promoter ◽  
Globin Gene Expression

Abstract To date, all of the chromosomal deletions that cause -thalassemia remove the structural  genes and/or their regulatory element (HS –40). A unique deletion occurs in a single family that juxtaposes a region that normally lies approximately 18-kilobase downstream of the human  cluster, next to a structurally normal -globin gene, and silences its expression. During development, the CpG island associated with the -globin promoter in the rearranged chromosome becomes densely methylated and insensitive to endonucleases, demonstrating that the normal chromatin structure around the -globin gene is perturbed by this mutation and that the gene is inactivated by a negative chromosomal position effect. These findings highlight the importance of the chromosomal environment in regulating globin gene expression.

scholarly journals Short stature and primary ovarian insufficiency possibly due to chromosomal position effect in a balanced X;1 translocation

2015 ◽  
Vol 8 (1) ◽  
Author(s):  
Rita Genesio ◽  
Angela Mormile ◽  
Maria Rosaria Licenziati ◽  
Daniele De Brasi ◽  
Graziella Leone ◽  
...  
Keyword(s):  
Short Stature ◽  
Position Effect ◽  
Primary Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Chromosomal Position ◽  
Chromosomal Position Effect

Chromosomal Position Effect and Aging

2010 ◽  
pp. 151-175
Author(s):  
Eric Gilson ◽  
Frédérique Magdinier
Keyword(s):  
Position Effect ◽  
Chromosomal Position ◽  
Chromosomal Position Effect

Abstract 3773: Myotrophin and the p53 Signaling Cascade in Cardiac Hypertrophy/Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Biswajit Das ◽  
David Young ◽  
Amit Vasanji ◽  
Sudhiranjan Gupta ◽  
Zoran Popovic ◽  
...  
Keyword(s):  
Heart Failure ◽  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Expression Profiles ◽  
Gene Array ◽  
Weight Ratio ◽  
Signaling Cascade ◽  
Mobility Shift ◽  
Transgenic Mouse Line ◽  
P53 Signaling

Myotrophin (Myo), a 12-kDa protein, stimulates myocyte growth and is a factor in initiating cardiac hypertrophy (CH). Cardiospecific overexpression of Myo in transgenic mice (Myo-Tg) induces hypertrophy that progresses to heart failure (HF). Oligonucleotide gene array revealed upregulation of a p53 homologue gene (EST- AI843106 ) in Myo-Tg mice during HF, indicating that p53 plays an important role during the transition of hypertrophy to HF. To dissect out the mechanisms of p53-mediated Myo-induced CH/HF, we developed a double-transgenic mouse line (p53 −/− /myo +/+ ) by crossing Myo-Tg mice with p53-null mice. The double transgenic mice showed a significant attenuation of cardiac mass compared to Myo-Tg mice (heart weight:body weight ratio; 5.2 ± 0.21 vs. 7.9 ± 0.58, p < 0.001) associated with improved cardiac function and downregulation of ANF expression, suggesting that hypertrophy induced by Myo overexpression is indeed mediated through p53. To elucidate the relationship between p53 and Myo-induced hypertrophy, we performed a Reverse-Transcription Real-Time PCR pathway array on heart tissues from p53 −/− /myo +/+ vs. Myo-Tg mice. A bioinformatic approach, Ingenuity Pathway Analysis TM (IPA), was used to analyze the selected up-/downregulated genes. The IPA network showed that among the up-/downregulated genes, Bcl2, Brca1, Cdkn1a and Myc occupy the nodal position, whereas E2f1 , Pmaip1 , Gadd45a and Pttg1 function as peripheral candidates. The expression profiles of some genes of the p53 pathway were validated by immunoblot analysis. Functional assignment of these selected candidate genes showed that Bcl2, E2f1 and FasL are related to CH/HF, but the function of Gadd45a, Pmaip1, and Vcan is still unknown. Apart from these p53 cascade members, we also found that other molecules (e.g., Jnk, Ras, NF-kB, Cyclin L, and Mek) may be involved in an intricate interplay to stimulate p53-mediated Myo-induced CH. Suppression of NF-kB activity (by electrophoresis mobility shift assay) in p53 −/− /myo +/+ mice compared to Myo-Tg mice indicated involvement of NF-kB, as predicted by IPA, in Myo/p53 cross-talk. Our data suggest that the p53 signaling cascade actively participates in progression of hypertrophy to HF, triggered by overexpression of myotrophin.

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