scholarly journals Mouse model of human beta zero thalassemia: targeted deletion of the mouse beta maj- and beta min-globin genes in embryonic stem cells.

1995 ◽  
Vol 92 (20) ◽  
pp. 9259-9263 ◽  
Author(s):  
D. J. Ciavatta ◽  
T. M. Ryan ◽  
S. C. Farmer ◽  
T. M. Townes
Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1846-1851 ◽  
Author(s):  
J Chang ◽  
RH Lu ◽  
SM Xu ◽  
J Meneses ◽  
K Chan ◽  
...  

We have disrupted the 5′ locus of the duplicated adult alpha-globin genes by gene targeting in the mouse embryonic stem cells and created mice with alpha-thalassemia syndromes. The heterozygous knockout mice (.alpha/alpha alpha) are asymptomatic like the silent carriers in humans whereas the homozygous knockout mice (.alpha/.alpha) show hemolytic anemia. Mice with three dysfunctional alpha-globin genes generated by breeding the 5′ alpha-globin knockouts (.alpha/alpha alpha) and the deletion type alpha-thalassemia mice (../alpha alpha) produce severe hemoglobin H disease and they die in utero. These results indicate that the 5′ alpha-globin gene is the predominant locus in mice, and suggest that it is even more dominant than its human homologue.


2006 ◽  
pp. 485-494
Author(s):  
Fumihiko Nishimura ◽  
Hayato Toriumi ◽  
Shigeaki Ishizaka ◽  
Toshisuke Sakaki ◽  
Masahide Yoshikawa

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1531-1533 ◽  
Author(s):  
Zhi Hong Lu ◽  
Jason T. Books ◽  
Richard M. Kaufman ◽  
Timothy J. Ley

Abstract The correction of mutant β-globin genes has long been a therapeutic goal for patients with β-thalassemia or hemoglobinopathies. The use of homologous recombination (HR) to achieve this goal is an attractive approach because it eliminates the need to include regulatory sequences in the therapeutic construct, and it eliminates mutagenesis induced by random integration. However, HR is a very inefficient process for gene correction, and its efficiency is probably locus dependent. The length of targeting arms is thought to be a determinant of targeting efficiency, so we compared the ability of standard (8-kb) versus very long (16-, 24-, and 110-kb) regions of homology to correct a mutant murine β-globin gene in embryonic stem cells. Increasing the length of the targeting sequences did not increase the efficiency of HR in this locus, suggesting that alternative approaches will be required to improve the efficiency of this approach for globin gene correction.


PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e33165 ◽  
Author(s):  
Ena Ray Banerjee ◽  
Michael A. Laflamme ◽  
Thalia Papayannopoulou ◽  
Michael Kahn ◽  
Charles E. Murry ◽  
...  

2002 ◽  
Vol 22 (2) ◽  
pp. 442-452 ◽  
Author(s):  
Mirit I. Aladjem ◽  
Luo Wei Rodewald ◽  
Chii Mai Lin ◽  
Sarah Bowman ◽  
Daniel M. Cimbora ◽  
...  

ABSTRACT The replication initiation pattern of the murine β-globin locus was analyzed in totipotent embryonic stem cells and in differentiated cell lines. Initiation events in the murine β-globin locus were detected in a region extending from the embryonic Ey gene to the adult βminor gene, unlike the restricted initiation observed in the human locus. Totipotent and differentiated cells exhibited similar initiation patterns. Deletion of the region between the adult globin genes did not prevent initiation in the remainder of the locus, suggesting that the potential to initiate DNA replication was not contained exclusively within the primary sequence of the deleted region. In addition, a deletion encompassing the six identified 5′ hypersensitive sites in the mouse locus control region had no effect on initiation from within the locus. As this deletion also did not affect the chromatin structure of the locus, we propose that the sequences determining both chromatin structure and replication initiation lie outside the hypersensitive sites removed by the deletion.


2010 ◽  
Vol 89 (8) ◽  
pp. 911-919 ◽  
Author(s):  
Nan-Kai Wang ◽  
Joaquin Tosi ◽  
Jennifer Mie Kasanuki ◽  
Chai Lin Chou ◽  
Jian Kong ◽  
...  

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