Targeting NHE6 gene expression identifies lysosome and neurodevelopmental mechanisms in a haploid in vitro cell model.

ABSTRACT: Christianson syndrome (CS) is an X-linked disorder resulting from loss-of-function (LoF) mutations in SLC9A6 encoding the endosomal Na+/H+ exchanger 6 (NHE6). CS presents with developmental delay, seizures, intellectual disability, nonverbal status, postnatal microcephaly, and ataxia. To define transcriptome signatures of NHE6 LoF, we conducted in-depth RNA-sequencing (RNA-seq) analysis on a haploid NHE6 null cell model. CRIPSR/Cas9 genome editing introduced multiple LoF mutations into SLC9A6 in the near haploid human cell line Hap1. Isogenic, paired parental controls were also studied. NHE6 mutant cell lines were confirmed to have intra-endosomal over-acidification as was seen in other NHE6 null cells. RNA-seq analysis was performed by two widely used pipelines: HISAT2-StringTie-DEseq2 an

SUBMITTER: Wu Q 

PROVIDER: S-EPMC10695175 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature