Table 1.
Mouse models to study the renin angiotensin system
| RAS Component | Gene Species | Mouse Strain | Notes | |
|---|---|---|---|---|
|
| ||||
| AGT | ||||
|
| ||||
| Knockout | Agt KO | Murine | C57BL/6 | Whole animal knockout19 |
| Agt KO | Murine | C57BL/6 | Whole animal knockout14 | |
| KAP-Agt-KO | Murine | C57BL/6N | Proximal tubule knockout122 | |
| Alb-Agt-Cre | Murine | C57BL/6N | Hepatocyte knockout22 | |
| KAP-Cre:Alb-Cre-Agt | Murine | C57BL/6N | Proximal tubule and hepatocyte knockout22 | |
| NEP25-KAP-Agt-KO | Murine | Podocyte injury model2 | ||
| Agt Copy Number Variants | Murine | 129xC57BL/6 | Changes in the level of Agt expression14 | |
| Agt+/−, Agt−/− | Murine | C57BL/6 | ||
| Overexpression | hRen+/hAng+ | Human | Mixed C57BL/6 | Double transgenic: human renin and human angiotensinogen16 |
| hAgt | Human | C57BL/6 × SJL/J | Whole animal overexpression17 | |
| Renin | ||||
|
| ||||
| Knockout | Ren2 KO | Murine | 129/Ola | Normal resting BP in presence of Renld alone30 |
| Ren-1 d KO | Murine | 129 | Abnormalities in the macula densa and juxtaglomerular cells31 | |
| Ren-1 c KO | Murine | Mixed C57:CBA Inbred C57 | Early death, significant hypotension, inability to concentrate urine33,34 | |
| AQP2-Cre | Murine | C57BL/6 | Collecting duct knockout36 | |
| Hox-b7-Cre | Murine | C57BL/6 | Collecting duct knockout of prorenin receptor109 | |
| Prorenin receptor KO | Murine | C57BL/6 | Renal tubular-specific prorenin receptor knockout38 | |
| Pax8-Cre | Murine | C57BL/6 | Nephron-specific knockout of Atp6ap2 pro-renin receptor39 | |
| nNOS/CreERT2 MD PRR KO | Murine | C57BL/6 | Macula densa knockout of pro-renin receptor40 | |
| Ren1d-Cre | Murine | C57BL6/J 129SvEv | Crossed to R26R or Z/EG reporter lines expressing β- galactosidase or GFP.42 Ren-1dCre mouse crossed to mT/mG reporter mice43 |
|
| ACE | ||||
|
| ||||
| Knockout | ACE1/1 | Murine | 129 × C57BL/6 | Low blood pressure, renal pathology50 |
| ACE N-KO | Murine | Mice lack N-domain of ACE53 | ||
| ACE C-KO | Murine | 129 × C57BL/6 | Mice lack C-domain of ACE54 | |
| ACE3/3 | Murine | 129 × C57BL/6 | Endothelial ACE knockout; ACE expression swapped to Albumin promoter58 | |
| ACE 8/8 | Murine | 129/C57BL/6 | Cardiac-restricted expression via a-myosin heavy chain promoter64 | |
| ACE 9/9 | Murine | 129 × C57BL/6 | ACE expression limited to the renal tubular epithelium63 | |
| ACE10/10 | Murine | 129 × C57BL/6 | ACE expression under control of c-fms promoter cassette: targeted to macrophage and macrophage- lineage cells 23 | |
| NeuACE | Murine | C57BL/6 | ACE expression under the control of the cfms promoter: targeted to neutrophils124 | |
| Overexpression | ACE copy number variants | Murine | C57BL/6 × 129/SvEv | One, two, or three functional copies of ACE gene68 |
| ACE2 | ||||
|
| ||||
| Knockout | ACE2−/y | Murine | Mixed 129 × C57BL/6 | Severe cardiac contractility disruption (phenotype lost in later studies)72 |
| ACE2−/y | Murine | Mixed 129 × C57BL/6 | Normal cardiac function and morphology73 | |
| ACE2−/y | Murine | Mixed 129/SvEv × C57BL/6 | Normal cardiac function and morphology74 | |
| ACE2−/y | Murine | 129/SvEv | No change in baseline BP74 | |
| ACE2−/y | Murine | C57BL/6 | Modest increase in baseline BP (~7 mmHg), no cardiac hypertrophy74 | |
| ACE2−/− | Murine | C57BL/6 | CRISPR-mediated frameshift mutation resulting ACE2 knock out125 | |
| Overexpression | ACE2-S680D Knock-in | Murine | C57BL/6 | A phosphomimic (S680D) mutant of ACE2125 |
| Synapsin-hACE2 | Human | C57BL/6 | Neuron-specific overexpression of ACE284 | |
| Synapsin-LoxP-hACE2 | Human | C57BL/6 × SJL/J | Cre-mediated neuron-specific overexpression of hACE2126 | |
| ROSA26 Ace2/Ace2 | Murine | Mixed 129/BL6 | Global ACE2 overexpression127 | |
| Nephrin-ACE2 | Human | FVB | Podocyte-specific overexpression of ACE282 | |
| hACE2 | Human | ICR | Driven by mouse ACE2 promoter87 | |
| hACE2 | Human | C57BL/6 × BALB/c mixed | Driven by CAG promoter; several lines with differing ACE2 expression91 | |
| K18-hACE2 | Human | C57BL/6J × SJL/J | Keratin 18 promoter; epithelial-specific expression88 | |
| HFH4-hACE2 | Human | C3H × C57BL/6 (C3B6) | HFH4 promoter—expression in multiple tissues90 | |
| PRCP & POP | ||||
|
| ||||
| KST302 | Murine | C57BL/6 | Global PRCP deficiency6 | |
| GST090 | Murine | FVB/N | Global PRCP deficiency6 | |
| ACE2 −/− /PRCP −/− | Murine | Global deficiency of ACE2 and PRCP5 | ||
| POP−/− | Murine | Global POP deficiency5 | ||
| AT1AR | ||||
|
| ||||
| Knockout | AT1AR KO | Murine | C57BL/6J | Severe hypotension97 |
| Pepck-Cre | Murine | 129/SvEv | Proximal tubule knockout; hypotensive103 | |
| KAP2-Cre | Murine | C57BL/6 | Proximal tubule knockout; hypotensive at baseline and with Ang II infusion107 |
|
| KAP2-AT1AR-N11G | Rat | C57BL/6J | Constitutively active form (N111G) of the rat AT1AR; active in the absence of Ang II107 | |
| Pod-Cre | Murine | Double knockout of AT1AR and Dyn1 and Dyn2110 | ||
| Hoxb7-Cre | Murine | 129/SvEv | Collecting duct knockout using Hoxb7-Cre promoter 109 | |
| AQP2-Cre | Murine | 129/SvEv | Principal cells of the collecting duct knockout108 | |
| AVP-Cre | Murine | C57BL/6J | Vasopressin-producing cells111 | |
| Nefh-Cre | Murine | Neuron-specific knockout128 | ||
| LepR-Cre | Murine | C57BL/6J | Leptin receptor-expressing cells113 | |
| ARP-Cre | Murine | C57BL/6J | Neurons expressing agouti-related peptide113 | |
| TH-Cre | Murine | Catacholaminergic cells114 | ||
| CRF-Cre | C57BL/6 | Cortocotropin-releasing factor neurons115 | ||
| CD4-Cre | Murine | 129/SvEv | T Lymphocytes117 | |
| LysM-Cre | Murine | 129/SvEv | Macrophages118 | |
| Lck-Cre | 129/SvEv | T Lymphocytes | ||
| OT-1-Cre | Murine | C57BL/6 | Antigen-specific CD8+ cells120 | |
| KISm22α-Cre | Murine | 129/SvEv | Vascular smooth muscle96 | |
RAS: Renin angiotensin system
Agt: Angiotensinogen
ACE: Angiotensin converting enzyme
ACE2: Angiotensin converting enzyme 2
PRCP: Prolylcarboxypeptidase
POP: Prolyloligopeptidase
AT1AR: Type 1 angiotensin receptor