Mettl14-deletion related liver damage and nuclear heterotypia

Liver-specific deletion of the N6-methyladenosine methyltransferase
complex member, Mettl14, in a mouse model demonstrates progressive liver
injury and marked nuclear heterotypia in hepatocytes. This phenotype
correlates with significant changes in the transcriptomic profile relative
to wild-type mouse liver, and changes in localization of the transcription
/ export machinery (TREX) complex as visualized by immunofluorescence.
Mettl14 deletion liver also exhibits exacerbated injury to toxicity-based
liver injury models, but shows no significant difference in regeneration
after physical injury as modeled by partial hepatectomy. Deletion of the
N6-methyladenosine recognizing proteins Ythdf1 and Ythdf2, both alone and
together, impacts response to toxicity-based liver injury. This affects
both liver mass regeneration and total mouse weight maintenance and
recovery post-surgery. Dual deletion of Ythdf1 and Ythdf2 in liver tissue
leads to liver damage in the steady state, and significantly exacerbated
damage after liver injury models relative to either Ythdf1 or Ythdf2
deletion alone.