- The Ace2 Knockout Mouse may be useful for COVID-19 research. Taconic and Lexicon have agreed to subsidize distribution of this Knockout Repository model (original model #TF3738) from a live colony as a contribution towards the global coronavirus response. Access is available to non-profit and for-profit institutions under modified Terms of Sale and subsidized pricing for use in COVID-19 and acute respiratory distress syndrome (ARDS) research. For uses outside of this field, please refer to the original product page for terms and pricing.
- ARDS is a serious complication of COVID-19 and present in a large percentage of COVID-19 deaths. ACE2 is protective against ARDS.
- Binding of viral spike SARS protein to ACE2 in mice downregulates ACE2 expression. Loss of ACE2 expression is associated with severe lung failure. Ace2 knockout mice have been used in ARDS and SARS research.
- This model does NOT carry the human ACE2 gene and thus is likely not permissive for infection by clinical isolates of SARS-CoV-2. Taconic has mice that express human ACE2 (hACE2) available now. Learn more about hACE2 mice for COVID-19 research and mouse-adapted SARS-CoV-2 viruses.
- The Ensembl database shows two isoforms of mouse ACE2 protein, one starting from Exon 2 of the gene (805 aa) and the second starting from Exon 6 (521 aa). The modification in this model targets the second exon (first coding exon) of Ace2, which is expected to result in a loss-of-function allele for the full-length isoform. It is unknown whether the second isoform will be produced in this model and if produced whether it is functional or not and can compensate for the loss of the full-length isoform. Correct targeting of the allele was confirmed by Southern blot analysis. Several publications have described phenotypic differences between wild type and homozygous mutant animals for this modification, consistent with interference with Ace2 function. It is recommended that researchers confirm loss-of-function status of the allele in their experimental system or tissue of interest.
- This line was generated on a mixed genetic background (B6;129S5). Due to the urgency of the research response to the COVID-19 pandemic, there is not sufficient time to backcross the Ace2 knockout mutation to an inbred genetic background. Researchers should be aware that phenotypes such as hypertension may vary for specific Ace2 knockout alleles on different inbred genetic backgrounds (Gurley and Coffman, 2007). Thus, as the result of a mixed genetic background the Ace2 knockout mice may show considerable inter-animal variation in phenotypes. It is recommended to carefully consider the impact of the genetic background when planning and interpreting experiments. Taconic can advise on backcross strategies and provide testing for marker-assisted speed congenic breeding. Generation of a fully congenic line can take 12-18 months.
- The murine Ace2 gene is located on the X chromosome. Female knockouts are homozygous (ko/ko). Male knockouts are hemizygous (ko/y). Other genotypes available for sale include female heterozygotes (ko/wt) and wild type littermates of both sexes (wt/wt females and wt/y males).
- Orders for "breeder packs" will be filled with 4 mutant mice of mixed sex and genotype for a single, low price. You may not specify desired genotype/sex for breeder pack orders. You may order individual mice and specify sex and genotype, but note that individual mouse pricing is higher and your order may be delayed. If you want wild type littermates for use in breeding with your breeder pack order, please order those wild types as individual mice. Breeder packs will not include any wild type mice.
- Possible mating formats and expected progeny are as below:
- Heterozygous female x hemizygous male: expected to produce homozygous and heterozygous females, hemizygous and wild type males.
- Heterozygous female x wild type male: expected to produce heterozygous and wild type females, hemizygous and wild type males.
- Homozygous female x hemizygous male: expected to produce homozygous females and hemizygous males. Will not provide a wild type control.
- Reproductive data including actual Mendellian ratios will be shared as it becomes available.
- Availability of study cohorts is very limited. We encourage you to set up breeding in-house or as a contract colony at Taconic.
angiotensin I converting enzyme (peptidyl-dipeptidase A) 2Synonyms:
2010305L05RikOrders by weight:
Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.Availability:
Gene Family: Protease
Genetic Background: The genetic background is mixed C57BL/6NTac, 129S5, and C57BL/6J (B6;129S5). Genome scan shows C57BL/6NTac is the predominant background strain (>90%).
Gene Accession Number: AB053181
Origin: The Ace2 Knockout Mouse was generated by Lexicon Pharmaceuticals via gene targeting in ES cells derived from the 129S5 inbred strain. The line was further bred to a C57BL/6J-Tyrc-Brd background and stored as cryopreserved sperm on a mixed genetic background. Taconic recovered the line in 2020 using C57BL/6NTac oocyte donors with that sperm. Additional crosses to C57BL/6NTac were performed to expand the line prior to intercrossing to generate homozygous female knockouts and hemizygous male knockouts. Taconic maintains breeding using heterozygous female knockouts x hemizygous male knockouts as well as heterozygous female knockouts by wild type males in order to generate all genotypes for sale.
Coat Color Loci: Carries segregating mix of alleles for non-agouti/white-bellied agouti (a, Aw), albino/non-albino (Tyrc-Brd, C) along with the black (B) allele.
Color: Various (black, black agouti, albino, are possible)
Relevant publications on other Ace2 knockout alleles:
- Tang, T.; Li, L.; Tang, J.; Li, Y.; Lin, W. Y.; Martin, F.; Grant, D.; Solloway, M.; Parker, L.; Ye, W.; Forrest, W.; Ghilardi, N.; Oravecz, T.; Platt, K. A.; Rice, D. S.; Hansen, G. M.; Abuin, A.; Eberhart, D. E.; Godowski, P.; Holt, K. H.; Peterson, A.; Zambrowicz, B. P.; Sauvage, F. J. D. A Mouse Knockout Library for Secreted and Transmembrane Proteins. Nature Biotechnology 2010, 28 (7), 749–755.
- Hung, Y.-H.; Hsieh, W.-Y.; Hsieh, J.-S.; Liu, F.-C.; Tsai, C.-H.; Lu, L.-C.; Huang, C.-Y.; Wu, C.-L.; Lin, C.-S. Alternative Roles of STAT3 and MAPK Signaling Pathways in the MMPs Activation and Progression of Lung Injury Induced by Cigarette Smoke Exposure in ACE2 Knockout Mice. International Journal of Biological Sciences 2016, 12 (4), 454–465.
- Wu, H.-T.; Chuang, Y.-W.; Huang, C.-P.; Chang, M.-H. Loss of Angiotensin Converting Enzyme II (ACE2) Accelerates the Development of Liver Injury Induced by Thioacetamide. Experimental Animals 2018, 67 (1), 41–49.
- Lin, C.-I.; Tsai, C.-H.; Sun, Y.-L.; Hsieh, W.-Y.; Lin, Y.-C.; Chen, C.-Y.; Lin, C.-S. Instillation of Particulate Matter 2.5 Induced Acute Lung Injury and Attenuated the Injury Recovery in ACE2 Knockout Mice. International Journal of Biological Sciences 2018, 14 (3), 253–265.
- Imai, Y.; Kuba, K.; Rao, S.; Huan, Y.; Guo, F.; Guan, B.; Yang, P.; Sarao, R.; Wada, T.; Leong-Poi, H.; Crackower, M. A.; Fukamizu, A.; Hui, C.-C.; Hein, L.; Uhlig, S.; Slutsky, A. S.; Jiang, C.; Penninger, J. M. Angiotensin-Converting Enzyme 2 Protects from Severe Acute Lung Failure. Nature 2005, 436 (7047), 112-116.
- Kuba, K.; Imai, Y.; Rao, S.; Gao, H.; Guo, F.; Guan, B.; Huan, Y.; Yang, P.; Zhang, Y.; Deng, W.; Bao, L.; Zhang, B.; Liu, G.; Wang, Z.; Chappell, M.; Liu, Y.; Zheng, D.; Leibbrandt, A.; Wada, T.; Slutsky, A. S.; Liu, D.; Qin, C.; Jiang, C.; Penninger, J. M. A Crucial Role of Angiotensin Converting Enzyme 2 (ACE2) in SARS Coronavirus-Induced Lung Injury. Nature Medicine 2005, 11 (8), 875-879.