Aph1c-flox Mouse

Aph1c is one of the genes encoding subunits of the gamma-secretase complex. Gamma-secretase is crucial for amyloid beta peptide release and is involved in Notch, N-Cadherin, and potentially other signaling pathways [1]. The gamma-secretase complex consists of at least four subunits: Presenilin, Aph1, Pen2, and Nicastrin. In rodents, Aph1c arose from a duplication of Aph1B [1].

In KO mouse models, Aph1C-/-mice survive into adulthood [1]. However, combined Aph1BC-/-deficiency (mimicking total Aph1B loss in human) causes a mild but significant reduction in amyloid beta precursor protein processing in selective regions of the adult brain [1]. Also, Aph1B/C-gamma-secretase complex is expressed in brain areas relevant to schizophrenia pathogenesis, and Aph1BC-/-mice show accumulation of Nrg1 fragments in the brain, along with pharmacological and behavioral abnormalities reversible by antipsychotic drugs [2].

In conclusion, Aph1c, as a part of the gamma-secretase complex, contributes to amyloid beta precursor protein processing in the brain and is involved in processes relevant to schizophrenia. Gene-knockout mouse models have been valuable in revealing these functions, helping us understand the biological roles of Aph1c in disease-related biological processes.