A number of criteria are applied when choosing the critical exon for a KOMP-CSD or EUCOMM allele, but not every gene can have all criteria fulfilled:

1. The critical exon(s) is selected so that its floxing (removal) by application of Cre produces a frameshift in every protein-coding transcript for the gene

2. The exon(s) is selected so that any residual transcript is subjected to NMD

3. The critical exon(s) is selected to be as 5-prime as possible, so that any residual protein product (if NMD doesn’t occurr) is non-functional.

4. The insertion of the lacZ-neo trap requires that the 5’ intron be large enough such that the trap can be placed without interfering with conserved / regulatory elements close to the splice sites. That is another constraint on the choice of critical exon(s)