Morphological Features of the Kidneys in <i>INSRR</i> Knockout Mice Under Bicarbonate Load

BACKGROUND: The insulin receptor-related receptor (IRR), a receptor tyrosine kinase, functions as a sensor of extracellular alkaline pH and is involved in renal bicarbonate excretion. High IRR expression has been detected in β-intercalated cells of the kidney, located in the distal tubules where bicarbonate secretion occurs. To create a new model for investigating sensitivity to pH changes, a unique INSRR knockout mouse line was developed on a C57BL/6 background. AIM: To analyze morphological changes in kidney tissue in INSRR knockout mice compared with wild-type animals under normal conditions and during metabolic alkalosis. METHODS: The study used littermate mice from a single generation, with genotypes confirmed by polymerase chain reaction. Two mouse lines were used in the experiment: INSRR knockout and wild-type. The animals were studied under two conditions—baseline and experimentally induced alkalosis. Morphometric analysis was performed on hematoxylin and eosin–stained kidney cryosections. The number of macrophages in kidney tissue was evaluated using immunohistochemical staining. RESULTS: Morphometric analysis revealed that INSRR gene knockout did not lead to significant pathological alterations in kidney structure. However, significant differences were observed in parenchymal thickness, glomerular area, and collecting duct diameter in sections taken at the level of the renal pelvis. Differences were observed both when comparing the two mouse lines under normal conditions and during experimental alkalosis. Additionally, kidney size in knockout mice was smaller than in wild-type animals. Immunohistochemical analysis revealed no statistically significant differences in the number of CD206-positive (anti-inflammatory) macrophages in the kidneys under either normal conditions or experimental alkalosis. CONCLUSION: Morphometric analysis of histological sections revealed increased parenchymal thickness in receptor tyrosine kinase knockout mice compared with wild-type animals under experimental alkalosis. Overall, knockout of the IRR receptor tyrosine kinase gene did not result in major pathological changes in kidney architecture. Thus, this genetically modified mouse line may serve as a model for physiological and molecular biological studies of metabolic alkalosis and its associated pathological processes.