LoxP-hACE2-CDS^tm Mice

Catalog Number: C001281

Strain Name: C57BL/6NCya-Ace2^{tm3(LoxP-hACE2-LoxP)}/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

Strain Description

Angiotensin-converting enzyme 2 (ACE2) is a member of the angiotensin-converting enzyme (ACE) family of dipeptidyl carboxypeptidases. ACE2 is expressed in a variety of human tissues and has a high affinity for angiotensin I (Ang I) and angiotensin II (Ang II) receptors. ACE2 catalyzes the cleavage of Ang I to angiotensin 1-9 (Ang 1-9) and Ang II to angiotensin 1-7 (Ang 1-7), which has vasodilatory and hypotensive effects ^[1]. ACE2 plays a role in regulating blood pressure, fluid balance, inflammation, cell proliferation, hypertrophy, and fibrosis, as well as in the regulation of cardiovascular and renal function and fertility ^[2]. ACE2 is also the common functional receptor for the spike protein of human coronaviruses HCoV-NL63, SARS-CoV, and SARS-CoV-2 ^[3]. However, due to species differences, the SARS-CoV-2 virus cannot bind to the ACE2 receptor of wild-type rodents ^[4-5]. Replacement of mouse Ace2 with human ACE2 by gene editing techniques resulted in humanized ACE2 mice (hACE2) that stably express human ACE2 receptors for COVID-19 studies.

This strain contains a loxP-hACE2 CDS-loxP gene expression cassette inserted at the endogenous  mouse Ace2 gene locus, which enables the regulation of human ACE2 gene (hACE2) expression by the mouse endogenous Ace2 regulatory element. When bred with relevant tissue-specific Cre mouse mating, knockout of the hACE2 gene can be achieved in specific tissues of the offspring mice. Homozygous LoxP-hACE2-CDS^tm mice are viable and fertile.

Strain strategy

 The loxP site-flanked hACE2’s coding sequence (CDS) was replaced with the endogenous mouse Ace2  sequence while retaining the sequence encoding the mouse ACE2 protein signal peptide.

Applications

• Cardiovascular function research;
• SARS-CoV-2 infection mechanism research;
• SARS-CoV-2 vaccine development evaluation;
• SARS-CoV-2 prevention and treatment drug screening evaluation;
• SARS-CoV-2 antibody drug development validation.

Announcements

The LSL-hACE2 cassette is integrated into the X chromosome in this strain. it is recommended to avoid breeding with Cre mice integrating with Cre recombinase cassette on the same chromosome.

References
[1]Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000 Sep 1;87(5):E1-9.
[2]Wang K, Gheblawi M, Oudit GY. Angiotensin Converting Enzyme 2: A Double-Edged Sword. Circulation. 2020 Aug 4;142(5):426-428.
[3]Zhang H, Rostami MR, Leopold PL, Mezey JG, O'Beirne SL, Strulovici-Barel Y, Crystal RG. Expression of the SARS-CoV-2 ACE2 Receptor in the Human Airway Epithelium. Am J Respir Crit Care Med. 2020 Jul 15;202(2):219-229.
[4]Bao L, Deng W, Huang B, Gao H, Liu J, Ren L, Wei Q, Yu P, Xu Y, Qi F, Qu Y, Li F, Lv Q, Wang W, Xue J, Gong S, Liu M, Wang G, Wang S, Song Z, Zhao L, Liu P, Zhao L, Ye F, Wang H, Zhou W, Zhu N, Zhen W, Yu H, Zhang X, Guo L, Chen L, Wang C, Wang Y, Wang X, Xiao Y, Sun Q, Liu H, Zhu F, Ma C, Yan L, Yang M, Han J, Xu W, Tan W, Peng X, Jin Q, Wu G, Qin C. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature. 2020 Jul;583(7818):830-833.
[5]Zheng J, Wong LR, Li K, Verma AK, Ortiz ME, Wohlford-Lenane C, Leidinger MR, Knudson CM, Meyerholz DK, McCray PB Jr, Perlman S. COVID-19 treatments and pathogenesis including anosmia in K18-hACE2 mice. Nature. 2021 Jan;589(7843):603-607.