Gmpr-flox Mouse

Gmpr, guanosine monophosphate reductase, is a nucleotide metabolism enzyme that decreases GTP pools by converting GMP to IMP, thus maintaining the cellular balance of adenine and guanine nucleotides [3,5]. It belongs to the IMPDH/GMPR family of (β/α)(8) barrel enzymes, sharing catalytic residues and ligand-binding properties with IMPDH [1]. In the body, it is involved in cellular metabolic pathways and is an important target for anti-leukemic agents [4].

Exome sequencing in the UK Biobank revealed novel Gmpr loss-of-function (LOF) variants with large effects on blood cell traits [2]. In a patient with a late-onset disorder of mitochondrial DNA maintenance, a novel heterozygous Gmpr variant was identified, causing aberrant splicing, decreased protein levels, and subtle changes in nucleotide homeostasis and mtDNA maintenance [5].

In conclusion, Gmpr is crucial for nucleotide metabolism and homeostasis. Findings from human genetic studies, such as those in the UK Biobank and in patients with mitochondrial DNA disorders, highlight its role in blood cell traits and mitochondrial DNA maintenance, providing insights into related disease mechanisms [2,5].