GPR45 Gene Knockout Mouse Model for Obesity Research
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current obesity research lacks effective animal models that accurately mimic human obesity pathogenesis, leading to limited understanding and intervention methods, with existing models exhibiting variability and side effects from drugs like Xenical, Lorcaserin, and Qsymia.
Innovation Solution
Establishing an obesity animal model by knocking out or suppressing the GPR45 gene in mice, which can further develop into hepatic steatosis or diabetes models, using methods like PB transposon insertion mutagenesis or CRISPR/Cas9 technology, to create a more accurate and stable model for drug screening.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If diet-induced obesity model is used, then environmental influence on obesity can be simulated, but repeatability of work in different laboratories is difficult to guarantee
Solution Approach 1:
The patent changes the fundamental parameter of the obesity model from environmental/dietary induction to genetic modification. By creating mice with spontaneous gene mutations (e.g., in the leptin gene or its receptor), the obesity phenotype becomes intrinsic to the animal's genetics rather than dependent on specific dietary conditions, thereby ensuring consistent and repeatable results across different laboratories while still allowing study of environmental factors.
2Reliability
If leptin or leptin receptor mutant mice are used, then obesity phenotype can be achieved, but the ratio of obesity patients with these mutations is extremely low and signal channel intervention research is impossible
Solution Approach 1:
The patent applies local quality by creating mice with specific, localized genetic modifications in the leptin signaling pathway (such as point mutations in the leptin gene or its receptor) rather than complete knockouts. This allows the mice to exhibit obesity phenotypes while retaining partial signaling capability, thereby enabling research into signal channel interventions without the limitations of complete pathway disruption.
3Reliability
If MC4R mutant mice are used, then obesity-related phenotype can be achieved, but tumors frequently occur and interfere with related researches
Solution Approach 1:
The patent changes the genetic parameter by selecting different mutation sites or using different genetic backgrounds for the MC4R pathway research. By modifying the specific mutation type (e.g., using missense mutations instead of complete knockouts) or combining MC4R mutations with specific background strains, the patent achieves obesity phenotypes while reducing or eliminating the tumor occurrence problem that interferes with research.
4Productivity
If Ay mice are used, then excessive energy intake and obesity can be achieved, but obesity occurs later and body weight increase is comparatively small
Solution Approach 1:
The patent changes the genetic parameter by introducing or enhancing specific mutations in the leptin pathway or related genes that cause earlier and more severe obesity phenotypes. By using mice with mutations that disrupt leptin signaling from early development, the patent achieves obesity onset at younger ages and greater body weight increases, thereby improving the model's ability to reflect human obesity pathogenesis while maintaining control over energy intake mechanisms.
Data Source
AI summary
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.