B6-hALK7 (hACVR1C) Mice

Catalog Number: C001709

Strain Name: C57BL/6NCya-Acvr1cem1(hACVR1C)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Heterozygote x Heterozygote

 

Strain Description

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 B6-hALK7 (hACVR1C) 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 (aa.1~25) 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.

 

Strain Strategy


Figure 1. Gene editing strategy of B6-hALK7 (hACVR1C) mice. The region from aa.27 in exon 2 to partial intron 2 of mouse Acvr1c will be replaced with "ACVR1C chimeric CDS-WPRE-BGH pA" cassette. The murine signal peptide (aa.1~25) of Acvr1c will be preserved.

 

Application

  • 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.

 

References
[1]Ibáñez CF. Regulation of metabolic homeostasis by the TGF-β superfamily receptor ALK7. FEBS J. 2022 Oct;289(19):5776-5797.
[2]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.
[3]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.