Sftpc-flox Mouse

Sftpc, which encodes surfactant protein C, is crucial for pulmonary development and homeostasis. Surfactant protein C is produced by alveolar type 2 (AT2) cells and is essential for maintaining normal lung function, such as reducing surface tension in the alveoli. Dysfunction in related pathways may lead to various lung-related issues [1,2,3,4,5,7]. Genetic models, like gene-edited mouse models, are valuable for studying Sftpc's function.

In a study using patient-specific induced pluripotent stem cells (iPSCs) carrying an SFTPC I73T mutation, mutant iAEC2s (differentiated from iPSCs) accumulated misprocessed and mistrafficked pro-SFTPC protein. This led to diminished AEC2 progenitor capacity, perturbed proteostasis, altered bioenergetic programs, metabolic reprogramming, and NF-κB pathway activation [1].

In another study, Sftpc-knockout (KO) mouse models were used to explore its role in neurodevelopmental disorders. Compound heterozygous variants of SFTPC in children with NDDs led to reduced Sftpc protein levels. Sftpc-knock-in (Sftpc-KI) mice carrying defective alleles showed reduced Sftpc expression in the lung and blood, along with impaired neurobehavioral performance and dysregulated proteins associated with neuroinflammation in the brain [6].

In conclusion, Sftpc is vital for normal lung function, especially in maintaining alveolar homeostasis. Model-based research, such as KO/CKO mouse models, has revealed its role in not only lung-related diseases like interstitial lung disease but also in unexpected areas like neurodevelopmental disorders. Understanding Sftpc's function through these models provides insights into disease mechanisms and potential therapeutic targets.