FINCA mouse as a tool to study mechanisms behind severe fibrosis and neurodegeneration

We have recently discovered a cerebropulmonary disease characterized by fibrosis, neurodegeneration and cerebral angiomatosis (FINCA) in children (MIM618278). Pathogenic variants were identified in a novel disease-causing gene, NHL repeat-containing protein 2 (NHLRC2). The children suffering from FINCA disease were found to have severe connective tissue formation in their lungs, degeneration of neuronal cells, and increased angiogenesis in the brain. The disease manifested at the age of two months, and progressed quickly. The research project of associate professor Hinttala focuses on understanding the pathophysiology of FINCA disease and the cellular pathways affected by NHLRC2 in order to identify solutions how to control reactions leading to severe fibrosis and/or neurodegeneration. The initial findings create a framework for the project to clarify the putative functional role of NHLRC2 by using state-of-the-art methodologies. A knock-in mouse model expressing FINCA mutation has been created utilizing CRISPR/Cas9 technology for in vivo studies of the project. Currently, the physiological function of this conserved protein has not been characterized in any species, nor has it been described as the primary cause for any other human disease. According to our findings, the protein has a fundamental role in tissue homeostasis, being important during development, but vital after birth.