Genes adapt to outsmart gene-targeting strategies in mutant mouse strains by skipping exons to reinitiate transcription and translation

Table 1 The KO-first gene disruption strategy results in conflicting phenotypes in homozygous mutant mice

Mice generated using KO-first strategy	Homozygous viable	Homozygous subviable	Homozygous lethal
Bbox1*	em1	tm1b
Caskin1	em1	tm1b
Cpsf3*		tm1b	tm1a
Dbn1*	em1	tm1b	tm1b
Dnmt3a*	tm1a	tm1b
Dppa1	tm1a	tm1b
Exoc3l2	tm1a		tm1b
Foxj3*	tm1a		tm1b
Ino80		tm1b	tm1a
Itm2c*	em2	tm1b
Kdm8*		tm1a	tm1b
Lmna*		tm1a	tm1b
Nxn*		tm1a	tm1b
Rundc1*		tm1b	tm1a
Slc20a2*	tm1a	tm1b
Tox3*	em1	tm1b
Zranb1	tm1a	tm1b

Analysis of 427 conditional-ready mouse strains generated using the KO-first strategy reveals that at least 4% of mouse strains show conflicting phenotypes. *Notably, 12 of 17 lethal/subviable genes express incomplete protein-coding sequences that could generate truncated proteins to potentially skew the phenotype of homozygous mutant mice

ISSN: 1474-760X