New application of casein kinase2-interacting protein-1 (CKIP-1) protein and coding gene thereof

A CKIP-1, 1. CKIP-1 technology, applied in the field of CKIP-1 protein and its coding gene, can solve problems such as decreased myocardial contractility and cardiac decompensation stage

Inactive Publication Date: 2012-11-28
SCI RES TRAINING CENT FOR CHINESE ASTRONAUTS +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although early myocardial hypertrophy is a compensatory mechanism for the heart to maintain effective cardiac output, persistent myocardial hypertrophy will lead to the heart entering a decompensated stage, re-expression of fetal genes ANP, BNP, β-MHC, etc., and subsequent irreversible events. Reversed cardiac hypertrophy and dilation, decreased contractility of the myocardium, leading to heart failure

Method used

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  • New application of casein kinase2-interacting protein-1 (CKIP-1) protein and coding gene thereof
  • New application of casein kinase2-interacting protein-1 (CKIP-1) protein and coding gene thereof
  • New application of casein kinase2-interacting protein-1 (CKIP-1) protein and coding gene thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1, Obtaining of CKIP-1 Gene Knockout Mice

[0052] 1. Obtaining CKIP-1 knockout mice

[0053] 1. Construction of targeting vector

[0054] The mouse CKIP-1 genome is a double-stranded DNA molecule shown in GENBANK ACCESSION NO.67220 (Gene ID: 67220, updated on 11-May-2012).

[0055] (1) The mouse CKIP-1 genome was double digested with restriction endonucleases NotI and XhoI, and a fragment of about 1.4 kb (fragment A) was recovered.

[0056] (2) Digest the ploxPI plasmid with restriction endonucleases NotI and XhoI to recover the vector backbone.

[0057] (3) Ligate the fragment recovered in step (1) with the vector backbone of step (2) to obtain a recombinant plasmid.

[0058] (4) The mouse CKIP-1 genome was double digested with restriction endonucleases EcoR I and SspI, and a fragment of about 9.6 kb was recovered.

[0059] (5) Digest the pBluescript SK(+) plasmid with restriction endonucleases EcoR I and SspI to recover the vector backbone.

[0060] (6) ...

Embodiment 2

[0084] Embodiment 2, KO mice and the comparison of parameters such as heart morphology and heart function of WT mice

[0085] 1. Changes in cardiac tissue morphology

[0086] The hearts of 2-month (or 8-month) KO mice and WT mice were taken respectively, and the myocardial structure and fibrosis degree were detected by HE staining, WGA staining and MTT staining after tissue sections.

[0087] see results figure 1 . figure 1 A is a photograph of HE staining, figure 1 B for figure 1 A partial enlarged view of A, figure 1 C is the photo of MTT staining, figure 1 D is a photograph of WGA staining. Compared with WT mice, heart volume and cardiomyocytes in KO mice were significantly larger at 2 months, and KO mice showed myocardial fibrosis at 8 months.

[0088] The morphological changes of the hearts of the empty vector control mice A were consistent with those of the WT mice.

[0089] 2. Changes in cardiac index

[0090] Take 3 KO mice of 2 months, 3 KO mice of 8 months, ...

Embodiment 3

[0127] Example 3. Confirmation of the role of CKIP-1 gene through the mouse cardiac hypertrophy model (KO mice and WT mice)

[0128] 1. Making a mouse model of myocardial hypertrophy (arch artery constriction)

[0129] KO mice and WT mice were subjected to the following experiments:

[0130] Model group (mouse cardiac hypertrophy model, represented by TAC): 8-week-old mice were anesthetized with tribromoethanol, connected to a small animal ventilator through tracheal intubation, and artificially ventilated. -3 intercostal space to open the thorax, separate the aortic arch and thread a thread under it, make the aorta constriction (Transverse aortic constriction, TAC) according to the uniform standard, and close the thorax.

[0131] Sham operation group (indicated by Sham): except that TAC was not performed, the rest of the operation procedures were completely the same as the model group.

[0132] Arch artery constriction is a routine method, and the literature describing arch...

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Abstract

The invention discloses new application of a casein kinase2-interacting protein-1 (CKIP-1) protein and a coding gene thereof. The invention provides the CKIP-1 protein, the coding gene of the CKIP-1 protein or application of plasmids containing the coding gene of the CKIP-1 protein in preparation of medicaments for preventing and/or treating myocardial hypertrophy; and the CKIP-1 protein is shown as a sequence 1 of a sequence table. The regulating effect of the CKIP-1 protein and the coding gene thereof in myocardial hypertrophy diseases is discovered, so that a new target and a new method are sought for diagnosis and treatment of the myocardial hypertrophy, and a foundation is laid for seeking clinical diagnosis and treatment of related diseases. The new application has great value for treating and preventing the myocardial hypertrophy.

Description

technical field [0001] The invention relates to a new application of CKIP-1 protein and its coding gene. Background technique [0002] Cardiovascular disease is one of the main diseases that endanger human health. The annual medical expenses of major cardiovascular diseases amount to 130 billion yuan, causing a huge economic burden to the society. In-depth study of the pathogenesis and molecular mechanism of cardiovascular diseases and the establishment of new prevention strategies and measures on this basis to reduce the mortality and disability rates of cardiovascular diseases are major basic scientific issues that life sciences need to solve. [0003] Cardiomyocyte hypertrophy is a pathological change associated with a variety of clinical cardiovascular diseases, and it is a major response of the heart to biomechanical stretch and neurohumoral stimulation. Although early myocardial hypertrophy is a compensatory mechanism for the heart to maintain effective cardiac output...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K48/00A61P9/00
Inventor 李英贤张令强贺福初孙乔凌树宽
Owner SCI RES TRAINING CENT FOR CHINESE ASTRONAUTS
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