Orientation of loxP sites in same direction leads to
Outcome of Cre-loxP recombination is dictated by relative orientation and location of loxP sites. When two loxP sites flank a DNA segment on same chromosome in direct repeat orientation, Cre-mediated synapsis brings sites together in parallel alignment, reciprocal exchange excises intervening DNA as circular product bearing one loxP and leaves single loxP at chromosomal locus. This deletion reaction is widely used for conditional knockouts using floxed alleles. Excision is essentially irreversible in absence of reintroduction, especially when circular product lacks replication origin and is lost during cell division.
Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 8: Cre-loxP Deletion by Directly Repeated Sites