Slc25a33-flox Mouse

Slc25a33, a member of the solute carrier family 25, encodes a mitochondrial pyrimidine nucleotide transporter [2]. It is crucial for mitochondrial DNA and RNA synthesis and breakdown by importing/exporting pyrimidine nucleotides into and from mitochondria [2].

In a study, deficiency of the mitochondrial protease YME1L led to inflammation in mouse retinas and cultured cells. This was due to YME1L's role in preserving pyrimidine pools by proteolysis of SLC25A33. YME1L deficiency drove the release of mtDNA and a cGAS-STING-TBK1-dependent inflammatory response, which required SLC25A33 and was suppressed upon pyrimidine pool replenishment [1]. Overexpression of SLC25A33 was sufficient to induce immune signalling by mtDNA [1].

In another context, in a zebrafish model, embryonic alcohol exposure altered the expression of slc25a33, which was associated with cardiomyopathy and diastolic dysfunction [4].

In diabetic retinopathy research, SLC25A33 was identified as an up-regulated key gene in gene co-expression network analysis, potentially serving as a biomarker and therapeutic target [3].

In conclusion, Slc25a33 plays an essential role in mitochondrial nucleotide transport and is involved in processes related to innate immunity, heart function, and diabetic retinopathy. Research using models such as gene-altered mouse retinas and zebrafish has provided insights into its function in these disease-related conditions.