A transgenic Ngal reporter mouse detects kidney injury in real timeTechnology #2172
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The Ngal reporter mouse allows for rapid real time assaying of kidney damage by linking expression of neutrophil gelatinase-associated lipocalin with a bioluminescent/fluorescent read-out. The Ngal fusion protein can be visualized in vivo or ex vivo, and has been shown to be induced three times faster than muscle-derived serum creatinine, which is the current clinical marker of kidney function. In mouse models of ischemic, infectious, and nephrotoxic kidney damage, kidney and urinary Ngal protein increased rapidly and dose-dependently. Thus, Ngal protein might be able to detect the earliest stages of renal injury caused by medications or diseases that would otherwise be clinically silent. Additionally, the Ngal mouse could present a more sensitive, cost-effective, and high-throughput method for the identification of novel therapeutics to mitigate kidney damage.
In vivo, real time monitoring of NGAL circumvents serial sample collections and mouse sacrifice and allows earlier detection of kidney damage.
Current methods for measuring serum creatinine require serial sampling of blood and urine, causing significant distress to the mouse. The marker itself is insensitive, as renal function must decrease below 50% for serum creatinine to be at a detectable level. Additionally, mouse models of ischemic kidney damage show that serum creatinine does not rise until 12 hours after the insult. The Ngal reporter mouse allows in vivo, real time bioluminescent/fluorescent imaging of the kidneys at an earlier time-point in disease progression. Furthermore, urinary Ngal secreted from thick ascending limb and collecting duct cells allows for another level of renal function monitoring.
- High-throughput in vivo screening of potential nephrotoxins in real time.
- High-throughput in vivo screening of potential reno-protective agents/therapeutics in real time.
- A more sensitive research model for renal disease progression, especially at earlier stages of injury.
- Allows real time monitoring of kidney injury by bioluminescence and fluorescence.
- Obviates the need for serial serum and urine collection.
- Levels of Ngal increase in response to kidney injury at a much earlier time point.
- Urinary Ngal is secreted from cells of the kidney tubule as another marker of injury.
- In the context of kidney injury, Ngal more specifically reflects changes in kidney anatomy, whereas creatinine can confuse the diagnosis by rising due to extra-renal factors.
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Tech Ventures Reference: IR 2172