Utilizing Transgenic Mice to Study Gene Regulation and Function

Author(s):  
Michael R. Blackburn ◽  
Rodney E. Kellems
1999 ◽  
Vol 59 (1) ◽  
pp. 33-39 ◽  
Author(s):  
L. B. Nielsen ◽  
S. P. A. McCormick ◽  
S. G. Young

Immunity ◽  
2006 ◽  
Vol 24 (1) ◽  
pp. 119
Author(s):  
Chen Dong ◽  
Shomyseh Sanjabi ◽  
Elizabeth Eynon
Keyword(s):  

2016 ◽  
Vol 291 (28) ◽  
pp. 14695-14705 ◽  
Author(s):  
Yun-Zi Liu ◽  
Xiaoyun Cheng ◽  
Ting Zhang ◽  
Sojin Lee ◽  
Jun Yamauchi ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
G. Chen ◽  
Y. Li ◽  
J. Tian ◽  
L. Zhang ◽  
P. Jean-Charles ◽  
...  

Cardiomyopathies are common cardiac disorders that primarily affect cardiac muscle resulting in cardiac dysfunction and heart failure. Transgenic mouse disease models have been developed to investigate the cellular mechanisms underlying heart failure and sudden cardiac death observed in cardiomyopathy cases and to explore the therapeutic outcomes in experimental animals in vivo. Echocardiography is an essential diagnostic tool for accurate and noninvasive assessment of cardiac structure and function in experimental animals. Our laboratory has been among the first to apply high-frequency research echocardiography on transgenic mice with cardiomyopathies. In this work, we have summarized our and other studies on assessment of systolic and diastolic dysfunction using conventional echocardiography, pulsed Doppler, and tissue Doppler imaging in transgenic mice with various cardiomyopathies. Estimation of embryonic mouse hearts has been performed as well using this high-resolution echocardiography. Some technical considerations in mouse echocardiography have also been discussed.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mai Terada ◽  
Kiyoshi Nobori ◽  
Yoshiko Munehisa ◽  
Manabu Kakizaki ◽  
Takayoshi Ohba ◽  
...  

Autophagy is an intracellular process in which proteins and organelles are transported in double-membrane vesicles called autophagosomes through the cytoplasm to lysosomes for degradation. The autophagosome acquires hydrolytic enzymes by fusing with the lysosome to generate an autolysosome. Constitutive autophagy in the heart under baseline conditions is a homeostatic mechanism for maintaining cardiomyocyte size and global cardiac structure and function. Upregulation of autophagy in various heart diseases, including cardiac hypertrophy and heart failure, is an adaptive response for protecting cells from hemodynamic stress. However, the detailed roles of autophagy in the heart remain unclear. LC3 is localized on the autophagosome membrane. Exogenously expressed GFP fused to LC3 (GFP-LC3) serves as an ideal molecular marker for autophagosome. Transgenic mice expressing GFP-LC3 (CAG-GFP-LC3) have been used to detect autophagy systemically. However, CAG-GFP-LC3 mice cannot distinguish autophagy-positive cardiomyocytes from other cells such as fibroblasts and smooth muscles in the heart and cannot detect autolysosome because GFP-LC3 loses fluorescence due to lysosomal acidic and degradative conditions. To resolve these problems, we have generated transgenic mice (αMyHC-mCherry-LC3) expressing mCherry fused to LC3 under the control of αmyosin heavy chain promoter instead of CAG promoter to detect autophagy only in cardiomyocytes. mCherry is an improved-monomeric red-fluorescence protein and does not lose fluorescence under acidic condition. Thus, αMyHC-mCherry-LC3 mice can detect not only autophagosome before fusion with lysosome but also autophagosome after fusion with lysosome. Moreover, we have crossed αMyHC-mCherry-LC3 mice with CAG-GFP-LC3 mice. Green signals showed autophagosome in non-cardiomyocytes. On the other hand, red signals showed autolysosome and double positive signals showed autophagosome in cardiacmyocytes. In conclusion, we have generated αMyHC-mCherry-LC3 mice to detect both autophagosome and autolysosome. The double transgenic mice cannot only detect autophagosome and autolysosome but also distinguish between them. This is an innovative method to examine the role of autophagy in cardiomyocytes.


Author(s):  
Steven E. Hyman ◽  
Doug McConnell

‘Mental illness: the collision of meaning with mechanism’ is based on the views of psychiatry that Steven Hyman articulated in his Loebel Lectures—mental illness results from the disordered functioning of the human brain and effective treatment repairs or mitigates those malfunctions. This view is not intended as reductionist as causes of mental illness and contributions to their repair may come from any source that affects the structure and function of the brain. These might include social interactions and other sources of lived experience, ideas (such as those learned in cognitive therapy), gene sequences and gene regulation, metabolic factors, drugs, electrodes, and so on. This, however, is not the whole story for psychiatry on Hyman’s view; interpersonal interactions between clinicians and patients, intuitively understood in such folk psychological terms as selfhood, intention, and agency are also critical for successful practice. As human beings who are suffering, patients seek to make sense of their lives and benefit from the empathy, respect, and a sense of being understood not only as the objects of a clinical encounter, but also as subjects. Hyman’s argument, however, is that the mechanisms by which human brains function and malfunction to produce the symptoms and impairments of mental illness are opaque to introspection and that the mechanistic understandings necessary for diagnosis and treatment are incommensurate with intuitive (folk psychological) human self-understanding. Thus, psychiatry does best when skillful clinicians switch between an objectifying medical and neurobiological stance and the interpersonal stance in which the clinician engages the patients as a subject. Attempts to integrate these incommensurate views of patients and their predicaments have historically produced incoherent explanations of psychopathology and have often led treatment astray. For example, privileging of folk psychological testimony, even when filtered through sophisticated theories has historically led psychiatry into intellectually blind and clinically ineffective cul-de-sacs such as psychoanalysis.


Science ◽  
2018 ◽  
Vol 361 (6403) ◽  
pp. 701-704 ◽  
Author(s):  
Jaechul Lim ◽  
Dongwan Kim ◽  
Young-suk Lee ◽  
Minju Ha ◽  
Mihye Lee ◽  
...  

RNA tails play integral roles in the regulation of messenger RNA (mRNA) translation and decay. Guanylation of the poly(A) tail was discovered recently, yet the enzymology and function remain obscure. Here we identify TENT4A (PAPD7) and TENT4B (PAPD5) as the enzymes responsible for mRNA guanylation. Purified TENT4 proteins generate a mixed poly(A) tail with intermittent non-adenosine residues, the most common of which is guanosine. A single guanosine residue is sufficient to impede the deadenylase CCR4-NOT complex, which trims the tail and exposes guanosine at the 3′ end. Consistently, depletion of TENT4A and TENT4B leads to a decrease in mRNA half-life and abundance in cells. Thus, TENT4A and TENT4B produce a mixed tail that shields mRNA from rapid deadenylation. Our study unveils the role of mixed tailing and expands the complexity of posttranscriptional gene regulation.


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