A novel mouse model for X-linked Alport syndrome induced by splicing mutation in the Col4a5 gene.

ABSTRACT: Alport syndrome is a hereditary kidney disease with significant variations in onset and prognosis. While 80-85% of cases are due to pathogenic variants in the COL4A5 gene, there is a notable lack of mouse models with Col4a5 mutations for basic research. Our research presents an 8-year-old child with Alport syndrome, exhibiting facial edema and abnormal urine. Next-generation sequencing revealed a c.1517-1G > T mutation in the intron sequence of the COL4A5 gene. Minigene experiments confirmed that this intronic mutation affects mRNA splicing. Using the CRISPR/Cas9 system, we developed a Col4a5-c.1517-1G > T mutant mouse model. Col4α5-deficient mice exhibited growth retardation and reduced lifespan. Renal function analysis indicated progressive deterioration, with high levels of BUN and crea

SUBMITTER: Ye Z 

PROVIDER: S-EPMC12086199 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature