Sarcolipin in atrium-specific gene targeting

Keyword(s):  
2018 ◽  
Vol 215 (12) ◽  
pp. 2984-2993 ◽  
Author(s):  
Kieran D. James ◽  
Emilie J. Cosway ◽  
Beth Lucas ◽  
Andrea J. White ◽  
Sonia M. Parnell ◽  
...  

The emigration of mature thymocytes from the thymus is critical for establishing peripheral T cell compartments. However, the pathways controlling this process and the timing of egress in relation to postselection developmental stages are poorly defined. Here, we reexamine thymocyte egress and test current and opposing models in relation to the requirement for LTβR, a regulator of thymic microenvironments and thymocyte emigration. Using cell-specific gene targeting, we show that the requirement for LTβR in thymocyte egress is distinct from its control of thymic epithelium and instead maps to expression by endothelial cells. By separating emigration into sequential phases of perivascular space (PVS) entry and transendothelial migration, we reveal a developmentally ordered program of egress where LTβR operates to rate limit access to the PVS. Collectively, we show the process of thymic emigration ensures only the most mature thymocytes leave the thymus and demonstrate a role for LTβR in the initiation of thymus emigration that segregates from its control of medulla organization.


2015 ◽  
Vol 14 (8) ◽  
pp. 783-791 ◽  
Author(s):  
Yuke Cen ◽  
Alessandro Fiori ◽  
Patrick Van Dijck

ABSTRACTCandida glabratais reported as the second most prevalent human opportunistic fungal pathogen in the United States. Over the last decades, its incidence increased, whereas that ofCandida albicansdecreased slightly. One of the main reasons for this shift is attributed to the inherent tolerance ofC. glabratatoward the commonly used azole antifungal drugs. Despite a close phylogenetic distance toSaccharomyces cerevisiae, homologous recombination works with poor efficiency inC. glabratacompared to baker's yeast, in fact limiting targeted genetic alterations of the pathogen's genome. It has been shown that nonhomologous DNA end joining is dominant over specific gene targeting inC. glabrata. To improve the homologous recombination efficiency, we have generated a strain in which theLIG4gene has been deleted, which resulted in a significant increase in correct gene targeting. The very specific function of Lig4 in mediating nonhomologous end joining is the reason for the absence of clear side effects, some of which affect theku80mutant, another mutant with reduced nonhomologous end joining. We also generated aLIG4reintegration cassette. Our results show that thelig4mutant strain may be a valuable tool for theC. glabrataresearch community.


2008 ◽  
Vol 130 (45) ◽  
pp. 14906-14907 ◽  
Author(s):  
Jeong-Hun Kang ◽  
Daisuke Asai ◽  
Jong-Hwan Kim ◽  
Takeshi Mori ◽  
Riki Toita ◽  
...  

genesis ◽  
2005 ◽  
Vol 41 (2) ◽  
pp. 73-80 ◽  
Author(s):  
Sha Li ◽  
Desheng Chen ◽  
Yves Sauvé ◽  
Jeremy McCandless ◽  
Yu-Jiun Chen ◽  
...  

2021 ◽  
Author(s):  
Yasuhiko Matsumoto ◽  
Tae Nagamachi ◽  
Asami Yoshikawa ◽  
Hideki Yamazaki ◽  
Yusuke Yamasaki ◽  
...  

Abstract Trichosporon asahii is a pathogenic fungus that causes severe, deep-seated fungal infections in neutropenic patients. Elucidating the infection mechanisms of T. asahii based on genetic studies requires a specific gene-targeting system. Here, we established an efficient gene-targeting system in a highly pathogenic T. asahii strain identified using the silkworm infection model. By comparing the pathogenicity of T. asahii clinical isolates in a silkworm infection model, T. asahii MPU129 was identified as a highly pathogenic strain. Using an Agrobacterium tumefaciens-mediated gene transfer system, we obtained a T. asahii MPU129 mutant lacking the ku70 gene, which encodes the Ku70 protein involved in the non-homologous end-joining repair of DNA double-strand breaks. The ku70 gene-deficient mutant showed higher gene-targeting efficiency than the wild-type strain for constructing a mutant lacking the cnb1 gene, which encodes the beta-subunit of calcineurin. The cnb1 gene-deficient mutant showed reduced pathogenicity against silkworms compared with the parental strain. These results suggest that an efficient gene-targeting system in a highly pathogenic T. asahii strain is a useful tool for elucidating the molecular mechanisms of T. asahii infection.


2010 ◽  
Vol 47 (2) ◽  
pp. 144-148
Author(s):  
Yuji Fukushima ◽  
Masaharu Sato ◽  
Haruo Matsuda ◽  
Shuichi Furusawa ◽  
Hiroyuki Horiuchi

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