Application of gpr45 gene

Inactive Publication Date: 2017-05-25
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

The present invention is about using a gene called GPR45 to screen drugs for treating obesity. The invention has discovered a connection between GPR45 and obesity, and has created an obesity mouse model by knocking out or suppressing the expression of GPR45. This model is more accurate and efficient than existing models, and can be used to screen drugs for treating obesity. Overall, the invention provides a more targeted approach for developing drugs for this condition.

Problems solved by technology

Obesity may cause lots of diseases, including Type 2 diabetes, hepatic steatosis, hypertension, coronary heart disease and various tumors, which jeopardizes health and living quality.
The essential mechanism of obesity is imbalanced individual energy metabolism.
Since the understanding about biological knowledge on occurrence and development mechanism of obesity is limited, there is still a shortage in commonly effective obesity intervention methods at present.
For example, it is usually difficult to perform diet and behavior correction for a long time, and effects for diet or behavior correction are always quite different individually.
Drugs such as Xenical, Lorcaserin and Qsymia have un-expected side effects on gastrointestinal and cardiovascular systems, and the effects are yet limited.
Therefore, after occurrence of obesity, it will always cause a lifelong influence and brings continuous harm to individuals, families and society.
However, for a long time, the selection of obese mouse models is extremely limited.
However, obesity caused through induction is closely related to the background of strains of mice and components and sources of fat and carbohydrate in feed, and there is a certain difficult to guarantee the repeatability of working in different laboratories.
In addition, the ratio of obesity patients with leptin or leptin receptor mutant is extremely low.
The lack of leptin signals also contributes to the impossibility to use these two kinds of mice for related signal channel intervention researches.
However, the interfere related researches are difficult to perform because of tumors frequently occur in MC4R mutant mice.

Method used

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  • Application of gpr45 gene
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  • Application of gpr45 gene

Examples

Experimental program
Comparison scheme
Effect test

embodiment 1

of GPR45 Inactivated Mutant Mice

[0070]GPR45 inactivated mutant mice can be obtained by changing a gene sequence or reducing gene expression through a method of inserting an exogenous DNG segment such as a transposon or a virus in a GPR45 gene sequence, or a chemical mutagenesis method such as ENU, or a physical mutagenesis method such as X-ray, or a gene targeting method based on an embryonic stem cell or CRISPR / Cas9 technology. These methods will cause loss-of-function mutations of GPR45 gene.

[0071]In this embodiment, the research strategy is as follows: firstly integrating transposon into a genome, causing precise corresponding gene mutants, then screening out individuals with certain specific phenotypes from the corresponding gene mutants and further detecting an insertion site of the transposon through a reverse PCR technology so as to investigate functions of a mutated gene.

[0072]We firstly adopted a mouse strain provided with a single copy and inserted with PB [Act-RFP] caused...

embodiment 3

ation Causes Hepatic Steatosiss

[0114]In obese patients, fat metabolism disorder usually cause excessive accumulation of fat in livers, resulting occurrence of hepatic steatosiss. In order to determine whether occurrence of hepatic steatosiss existed in GPR45PB1 mutant mice or not, we dissected livers of the mutant mice and found that the weight of the livers of 6-month-old female homozygote mutant mice and male homozygote mutant mice was respectively increased by 14.4% and 32.2% relative to the weight of the livers of wild type mice. The increase of the weight of the livers indicated that there was a possibility of fat accumulation. In order to further determine that the mutant mice had a phenotype of hepatic steatosiss, we stained frozen slices of livers of 9-month-old mice by using a dye, i.e., oil red O which can stain fat in red (as shown in FIG. 4). Results indicated that more fat drops were accumulated in liver cells of the mutant mice. The above-mentioned results indicated th...

embodiment 7

rtant of GPR45 or Transgenic Expression Results in Reduced Obesity of Mice

[0119]To sum up from embodiments 1-6, we observed that GPR45PB1 and GPR45PB2 mutant mice had the similar phenotypes of obesity and glucose intolerance. Therefore, we deduced that blocking of expression of GPR45 was closely related to the phenotype of obesity of the mutant mice. In order to further prove this assumption, we enabled transgenic mice carrying PBase transposase to mate with GPR45PB1 homozygote mutant mice, obtained GPR45PB1 homozygote mutant mice carrying PBase genes, then enabled the GPR45PB1 homozygote mutant mice carrying PBase genes to mate with GPR45PB1 homozygote mutant mice and obtained a GPR45 reverse mutant strain (GPRrev / GPRrev) which was produced by precise removal of the inserted PB transposon.

[0120]A method for establishing transgenic mice carrying PB transposase was as follow:

[0121](1) For details of a method for establishing Act-PBase, see Efficient transposition of the piggyBac (PB)...

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Abstract

The present invention relates to the field of biotechnology, in particular to application of a GPR45 gene. The present invention discloses, for the first time, a correlation between GPR45 and obesity and also discloses that obesity may be caused if the GPR45 gene is knocked out or the expression of the GPR45 gene is reduced. Moreover, an obese mouse model is established by adopting a method of blocking the expression of the GPR45 gene for the first time, which is more similar to the mechanism underlying the obesity of human, is thus an ideal model for obesity basis and clinical application researches and can be well applied in screening of drugs for treating obesity.

Description

FIELD OF THE INVENTION[0001]The present invention relates the field of biotechnology, in particular to application of a GPR45 gene.BACKGROUND OF THE INVENTION[0002]Obesity may cause lots of diseases, including Type 2 diabetes, hepatic steatosis, hypertension, coronary heart disease and various tumors, which jeopardizes health and living quality. Obesity of children and teenagers may further influence adolescent development and sexual maturity. According to statistics of WHO (World Health Organization), 35% of adults in the world are overweight (BMI≧25), more than 10% of adults are obese (BMI≧30) and at least 2.8 million people die from obesity or overweight each year. With the change of lifestyles, obese and overweight populations in China increase rapidly. By calculating according to WHO standards, in 2013, about 28% of adults were overweight, 4-5% of adults were obese and the total number of obese populations had taken the second place in the world in China. By predicting accordin...

Claims

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Application Information

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IPC IPC(8): A61K49/00A01K67/027
CPCA61K49/0008A01K67/0276A01K2267/0362A01K2217/075A01K2227/10A01K2217/052A01K2217/056A01K2217/206A01K2227/105C12N2800/90
Inventor WU, XIAOHUIXU, TIANHAN, MINCUI, JINGLI, TONGRUI
Owner FUDAN UNIV
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