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hALK7(ACVR1C) Mouse
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hALK7(ACVR1C) Mouse
제품명
hALK7(ACVR1C) Mouse
제품 ID
C001709
품종 계통
C57BL/6NCya-Acvr1cem1(hACVR1C)/Cya
Backgroud
C57BL/6NCya
상태
이 마우스 계통을 논문에서 사용할 경우, “hALK7(ACVR1C) Mouse (카탈로그 번호 C001709)은 Cyagen에서 구입하였습니다.”라고 명시해 주시기 바랍니다.
Metabolic Target Humanized Mouse Models
Obesity and Diabetes Mellitus
Small Nucleic Acids
구매 가능한 제품 종류
연령
Genotype
성별
수량
표준 제공 조건은 최소 3마리의 이형접합(heterozygous) 보균자를 보장합니다. 동형접합(homozygous) 보균자 및/또는 특정 성별에 대한 브리딩 서비스도 제공됩니다.
가격 문의
Metabolic Target Humanized Mouse Models
Obesity and Diabetes Mellitus
Small Nucleic Acids
기본 정보
검증 데이터
관련 자료
기본 정보
유전자명
유전자 별칭
ALK7, ACVRLK7
NCBI ID
염색체
Chr 2
MGI ID
Datasheet
품종 계통 설명
The activin A receptor type 1C (ACVR1C), also known as activin receptor-like kinase 7 (ALK7), is a crucial type I serine/threonine kinase receptor belonging to the transforming growth factor-β (TGF-β) superfamily signaling pathway. Upon binding ligands such as activin AB, activin B, and NODAL, ACVR1C initiates intracellular signaling cascades by phosphorylating downstream SMAD2 and SMAD3 transcription factors, thereby regulating diverse cellular processes including cell differentiation, proliferation, apoptosis, and metabolic homeostasis [1]. ACVR1C exhibits a broad expression profile across various tissues, with notable enrichment in adipose tissue, pancreas, heart, and specific brain regions, suggesting its pleiotropic roles in maintaining tissue function [2]. Dysregulation of ACVR1C signaling has been implicated in a range of metabolic disorders, including obesity and type 2 diabetes, as well as in the pathogenesis of certain cancers like retinoblastoma, highlighting its significance as a potential therapeutic target for these conditions [3].
The hALK7(ACVR1C) mouse is a humanized model constructed using gene editing technology, where the region from aa.27 in exon 2 to partial intron 2 of mouse Acvr1c was replaced with "ACVR1C chimeric CDS-WPRE-BGH pA" cassette. The murine signal peptide of Acvr1c was preserved. This model can be used for studying the pathological mechanisms and therapeutic approaches of metabolic disorders such as obesity and type 2 diabetes, and certain cancers like retinoblastoma, and for the development of ACVR1C-targeted drugs.
Reference
Ibáñez CF. Regulation of metabolic homeostasis by the TGF-β superfamily receptor ALK7. FEBS J. 2022 Oct;289(19):5776-5797.
Zhao M, Okunishi K, Bu Y, Kikuchi O, Wang H, Kitamura T, Izumi T. Targeting activin receptor-like kinase 7 ameliorates adiposity and associated metabolic disorders. JCI Insight. 2023 Feb 22;8(4):e161229.
Asnaghi L, White DT, Key N, Choi J, Mahale A, Alkatan H, Edward DP, Elkhamary SM, Al-Mesfer S, Maktabi A, Hurtado CG, Lee GY, Carcaboso AM, Mumm JS, Safieh LA, Eberhart CG. ACVR1C/SMAD2 signaling promotes invasion and growth in retinoblastoma. Oncogene. 2019 Mar;38(12):2056-2075.
변형 전략
The region from aa.27 in exon 2 to partial intron 2 of mouse Acvr1c was replaced with ACVR1C chimeric CDS-WPRE-BGH pA cassette. The murine signal peptide of Acvr1c was preserved.

Figure 1. Gene editing strategy of hALK7(ACVR1C) mice.
ACVR1C chimeric CDS: Extracellular Domain of Human ACVR1C + Transmembrane and Cytoplasmic Domain of Mouse Acvr1c
응용 분야
ACVR1C-targeted drug screening, development, and evaluation;
Research on the pathological mechanisms and therapeutic approaches of metabolic disorders such as obesity and type 2 diabetes;
Research on the pathological mechanisms and therapeutic approaches of certain cancers, like retinoblastoma.
검증 데이터
1. Gene Expression
RT-qPCR results showed that human ALK7 mRNA was expressed in the gWAT, iWAT, and GAS of homozygous hALK7(ACVR1C) mice.

Figure 2. Gene expression analysis of gonadal white adipose tissue (gWAT), inguinal white adipose tissue (iWAT), and gastrocnemius muscle (GAS) in homozygous hALK7(ACVR1C) mice and wild-type (WT) mice (7~8 weeks old, homozygous; WT: n=3♂/4♀,hALK7: n=3♂/5♀).
2. Blood Lipid & Hepatic Injury Levels (Blood Biochemical Assay)
Blood biochemical assay results showed that compared with WT mice, hALK7(ACVR1C) mice exhibited no significant differences in hepatic injury levels (ALT, AST) and blood lipid profiles (TC, LDL-C). Minor differences were observed in TG and HDL-C levels, while all indices remained within normal physiological ranges. (Data are presented as mean±SD, P values were calculated by t-test, *P<0.05)

Figure 3. Blood lipid and liver function indices in homozygous hALK7(ACVR1C) mice and wild-type (WT) mice (7~8 weeks old, homozygous; WT: n=3♂/4♀, hALK7: n=3♂/5♀).
*ALT: Alanine Aminotransferase; AST: Aspartate Aminotransferase; TG: Triglyceride; TC: Total Cholesterol; HDL-C: High-density Lipoprotein Cholesterol; LDL-C: Low-density Lipoprotein Cholesterol.
3. Pharmacodynamic Validation of Positive Control
Mice were divided into a vehicle control group (saline) and a positive control group (single subcutaneous injection of AD-2640060.02 at 3 mg/kg). Seven days post-administration, mice were euthanized, and inguinal white adipose tissue (iWAT), mesenteric white adipose tissue (mWAT), and gonadal white adipose tissue (gWAT) were harvested. Human ALK7 mRNA levels were quantified via RT-qPCR. Compared to the vehicle group, the positive control group exhibited a decreasing trend in human ALK7 mRNA expression across iWAT, mWAT, and gWAT.

Figure 4. Effect of the positive control on human ALK7 mRNA expression in adipose tissues of hALK7(ACVR1C) mice.
hALK7(KI/KI)+vehicle: n=1♂1♀; hALK7(KI/KI)+AD-2640060.02 (3mg/kg): n=1♂2♀
*Data provided by a Cyagen Biosciences partner.
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