Genome wide transcriptional changes underlie gradual and recurrent adaptation to protein malnutrition in zebrafish

Loss of LRE function causes severe stunting and poor survival due to protein malnutrition. Previously, we reported that loss of Plasmolipin (pllp), an endosomal membrane protein highly expressed in LREs, impairs LRE differentiation and dietary protein absorption, resulting in marked reduction in survival rates.

Raising pllp homozygous mutants surviving to adulthood and in-crossing them for multiple generations resulted in their adaptation to malnutrition, with pllp mutants showing robust suppression of survival deficits. To uncover mechanisms underlying this adaptive response, we conducted transcriptome profiling and protein absorption assays to compare the older adapted pllp allele with genetically related wild type (WT) fish and a newly generated pllp mutant allele.