App Conditional Knockout mouse models

App encodes amyloid precursor protein, the mouse ortholog of human APP, a type I transmembrane glycoprotein with E1 and E2 ectodomain modules that is either cleaved by ADAM10 within the Aβ sequence, precluding amyloid, or processed sequentially by BACE1 and the presenilin-containing γ-secretase complex to liberate Aβ40, Aβ42 and the AICD transcriptional fragment. Familial Alzheimer alleles act by shifting that competition: Swedish KM670/671NL enhances BACE1 cleavage, London V717I raises the Aβ42 to Aβ40 ratio, Arctic E22G accelerates protofibril assembly, and Icelandic A673T is protective. Rodent Aβ differs from human at three residues (Arg5, Tyr10, His13) and aggregates poorly, so humanizing the Aβ-coding exons in place, rather than transgenic overexpression, is the design that preserves endogenous promoter control and copy number. Aplp1 and Aplp2 compensate broadly, and App with Aplp2 double nulls die perinatally, so plan compound genetics when synaptic and neuromuscular endpoints accompany plaque and cerebral amyloid angiopathy readouts.

A floxed App allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.