Name: huINHBE Mouse
Brand: 싸이아젠(Cyagen)
SKU: C001533

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huINHBE Mouse

제품명

huINHBE Mouse

제품 ID

C001533

품종 계통

C57BL/6NCya-Inhbe^tm1(hINHBE)/Cya

Backgroud

C57BL/6NCya

상태

이 마우스 계통을 논문에서 사용할 경우, “huINHBE Mouse (카탈로그 번호 C001533)은 Cyagen에서 구입하였습니다.”라고 명시해 주시기 바랍니다.

HUGO-GT Humanized Models

Metabolic Target Humanized Mouse Models

Cytokine Gene Humanized Mouse Models

Fat Reduction and Muscle Gain

Small Nucleic Acids

구매 가능한 제품 종류

연령

Genotype

성별

수량

가격 문의

HUGO-GT Humanized Models

Metabolic Target Humanized Mouse Models

Cytokine Gene Humanized Mouse Models

Fat Reduction and Muscle Gain

Small Nucleic Acids

기본 정보

검증 데이터

The studies conducted by Alnylam Pharmaceuticals and the Regeneron Genetics Center (RGC), respectively, revealed the close relationship between INHBE and fat regulation. The research demonstrated that rare loss-of-function variants in INHBE may protect the liver from the impact of inflammation, abnormal blood lipids, and type 2 diabetes by promoting healthy fat storage. Patients carrying such mutations exhibit more normal fat distribution, significantly reduced abdominal fat, improved metabolic conditions, and a decreased risk of cardiovascular diseases and type 2 diabetes ^[2-4]. These findings suggest that INHBE is a liver-specific negative regulator of fat storage. Inhibiting the expression of INHBE genes and proteins may be a potential strategy for treating metabolic disorders related to improper fat distribution and storage. Consequently, several small nucleic acid pharmaceutical companies, including Alnylam Pharmaceuticals, Arrowhead Pharmaceuticals, and Wave Life Sciences, are currently developing RNA interference (RNAi) drugs targeting INHBE to treat conditions such as obesity ^[5-7].

RNAi drugs primarily include small interfering RNA (siRNA) and antisense oligonucleotides (ASO). siRNA targets and degrades specific mRNA, while ASO binds to the target mRNA, preventing its translation or inducing its degradation, thereby inhibiting the expression of the target gene. Considering the genetic differences between humans and animals, humanizing mouse genes can accelerate the clinical development of RNAi therapies targeting human INHBE. This strain is a mouse Inhbe gene humanized model and can be used to study therapies targeting INHBE for obesity. The homozygous huINHBE mice are viable and fertile. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate hot mutation models based on this strain and provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields.

Reference

Sugiyama M, Kikuchi A, Misu H, Igawa H, Ashihara M, Kushima Y, Honda K, Suzuki Y, Kawabe Y, Kaneko S, Takamura T. Inhibin βE (INHBE) is a possible insulin resistance-associated hepatokine identified by comprehensive gene expression analysis in human liver biopsy samples. PLoS One. 2018 Mar 29;13(3):e0194798.

Akbari P, Sosina OA, Bovijn J, Landheer K, Nielsen JB, Kim M, Aykul S, De T, Haas ME, Hindy G, Lin N, Dinsmore IR, Luo JZ, Hectors S, Geraghty B, Germino M, Panagis L, Parasoglou P, Walls JR, Halasz G, Atwal GS; Regeneron Genetics Center; DiscovEHR Collaboration; Jones M, LeBlanc MG, Still CD, Carey DJ, Giontella A, Orho-Melander M, Berumen J, Kuri-Morales P, Alegre-Díaz J, Torres JM, Emberson JR, Collins R, Rader DJ, Zambrowicz B, Murphy AJ, Balasubramanian S, Overton JD, Reid JG, Shuldiner AR, Cantor M, Abecasis GR, Ferreira MAR, Sleeman MW, Gusarova V, Altarejos J, Harris C, Economides AN, Idone V, Karalis K, Della Gatta G, Mirshahi T, Yancopoulos GD, Melander O, Marchini J, Tapia-Conyer R, Locke AE, Baras A, Verweij N, Lotta LA. Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes. Nat Commun. 2022 Aug 23;13(1):4844.

Deaton AM, Dubey A, Ward LD, Dornbos P, Flannick J; AMP-T2D-GENES Consortium; Yee E, Ticau S, Noetzli L, Parker MM, Hoffing RA, Willis C, Plekan ME, Holleman AM, Hinkle G, Fitzgerald K, Vaishnaw AK, Nioi P. Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity. Nat Commun. 2022 Jul 27;13(1):4319.

Adam RC, Pryce DS, Lee JS, Zhao Y, Mintah IJ, Min S, Halasz G, Mastaitis J, Atwal GS, Aykul S, Idone V, Economides AN, Lotta LA, Murphy AJ, Yancopoulos GD, Sleeman MW, Gusarova V. Activin E-ACVR1C cross talk controls energy storage via suppression of adipose lipolysis in mice. Proc Natl Acad Sci U S A. 2023 Aug 8;120(32):e2309967120.

Arrowhead Pharmaceuticals. (2024). Arrowhead Pharmaceuticals Reports Fiscal 2024 First Quarter Results. Retrieved April 5, 2024, from https://arrowheadpharma.com/news-press/arrowhead-pharmaceuticals-reports-fiscal-2024-first-quarter-results-2/

Alnylam Pharmaceuticals. (2024). Harnessing Human Genetics to Power the Next Wave of RNAi Therapeutics. Retrieved April 5, 2024, from https://news.alnylam.com/rnai/articles/harnessing-human-genetics-power-next-wave-rnai-therapeutics

Wave Life Sciences. (2024). Research and Development. Retrieved April 5, 2024, from https://wavelifesciences.com/pipeline/research-and-development/

변형 전략

The sequences from the ATG start codon to 3'UTR of mouse Inhbe were replaced with the sequences from the ATG start codon to 3'UTR of human INHBE.

Figure 1. Gene editing strategy of huINHBE mice.

응용 분야

Obesity and metabolic diseases associated with improper fat distribution and storage;

Development of human INHBE-targeted therapies.

검증 데이터

1. Detection of human INHBE gene and mouse Inhbe gene expression

（1）The huINHBE mice successfully express the human gene

Figure 2. Expression of human INHBE gene and mouse Inhbe gene in the liver of 6-week-old homozygous huINHBE mice and wild-type (WT) mice. RT-qPCR results revealed significant expression of the human INHBE gene in both male and female huINHBE mice livers, while no expression of the human INHBE gene was detected in wild-type mice. In wild-type mice liver, expression of the mouse Inhbe gene was present, whereas huINHBE mice did not exhibit expression of the mouse Inhbe gene. ND: Not detected.

（2）Monitoring of gene expression levels across different ages (in weeks)

Figure 3. Fluctuations in hepatic gene expression levels between homozygous huINHBE mice and wild-type (WT) mice at different ages (in weeks). Liver tissues were collected from 5 mice per group at 6, 10, 15, and 20 weeks of age, respectively. The expression levels of the human gene and the murine gene were detected by RT-qPCR. The results showed that the expression levels of human INHBE mRNA and mouse Inhbe mRNA fluctuated among mice of different ages; however, the difference in CT values was negligible (ranging from 24 to 25). (Data are presented as mean ± SD; n = 5; P-values were calculated by two-way ANOVA; letters a, b, and c indicate P < 0.01. Groups with the same letter indicate no significant difference between them, while groups with different letters indicate a significant difference between them.)

2. Detection of human INHBE protein expression

Figure 4. Western blot results of human INHBE protein expression in the serum of 6-week-old homozygous huINHBE mice and wild-type (WT) mice*. The results demonstrate significant expression of human INHBE protein in both male and female huINHBE mice serum. Additionally, due to the potential cross-reactivity of the antibody with both human and mouse INHBE proteins, INHBE-positive bands were also detected in wild-type mouse samples. *The INHBE antibody used in this assay is from Novus Biologicals (product number H00083729-B01P). Due to the cross-reactivity of antibodies, it is not recommended to use this detection method for quantitative analysis in long-term pharmacodynamic experiments.

3. Small interfering RNA (siRNA) drug significantly reduces the expression of the human INHBE gene in the liver of huINHBE mice.

（1）Case Ⅰ

Figure 5. Human INHBE gene expression in the liver of 7-week-old female homozygous huINHBE mice after subcutaneous injection of siRNA drugs*. A single dose of siRNA drug (1 mg/kg) was administered, and liver tissue was collected for RT-qPCR analysis 5 days later. The results demonstrate a significant reduction in human INHBE gene expression in the liver of huINHBE mice treated with the siRNA drug. *The siRNA drug was provided by Cyagen’s customer and targets the human INHBE gene to decrease its expression.

（2）Case Ⅱ

Figure 6. Detection of human INHBE gene expression in the liver of huINHBE mice after siRNA drug treatment*. A single subcutaneous injection of siRNA drugs targeting the human INHBE sequence was administered at a dose of 3 mg/kg. Mouse liver tissues were collected on Day 7 (D7) and Day 14 (D14) after drug treatment, respectively, and the mRNA level of human INHBE gene in the liver was detected by RT-qPCR. Results showed that compared with the Vehicle group, the expression of human INHBE mRNA in the liver of huINHBE mice was significantly reduced after siRNA drug treatment, indicating that the small nucleic acid drug could significantly inhibit the expression of human INHBE mRNA in humanized mice. (n=3, data presented as Mean±SD, P values calculated by TWO-WAY ANOVA, *P<0.05, **P<0.01, ***P<0.001) *This data was provided by the client.

huINHBE Mouse

기본 정보

검증 데이터

관련 자료

유전자명

유전자 별칭

NCBI ID

염색체

MGI ID

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Datasheet

품종 계통 설명

Reference

변형 전략

응용 분야

1. Detection of human INHBE gene and mouse Inhbe gene expression

2. Detection of human INHBE protein expression

3. Small interfering RNA (siRNA) drug significantly reduces the expression of the human INHBE gene in the liver of huINHBE mice.

관련 제품

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