Akr1cl-KO Mouse

Akr1cl encodes a member of the aldo-keto reductase 1C subfamily. Its product functions as an NADPH-dependent reductase involved in the metabolism of prostaglandins, with a key role in the specific reduction of prostaglandin (PG) D2 and oxidation of 9α,11β-PGF2 in the reverse reaction. This enzyme activity likely impacts related physiological pathways in mammals [1].

The recombinant AKR1CL shows strict substrate specificity, only acting on PGD2 and 9α,11β-PGF2 among tested substrates, while other PGs, steroids, non-steroidal carbonyls and alcohols are not substrates. Its activity is inhibited by several compounds like estradiol. Akr1cl mRNA is highly expressed in mouse testis, ovary and adrenal gland, and at lower levels in other tissues. Site-directed mutagenesis of P85 in AKR1CL to W (as in other AKR1C subfamily enzymes) broadens substrate specificity, highlighting the role of P85 in substrate specificity [1].

In conclusion, Akr1cl encodes an enzyme with strict substrate specificity for PGD2 and 9α,11β-PGF2 in mammals. The study of Akr1cl, including through mutagenesis in a model-based research context, helps to understand its role in prostaglandin metabolism and potentially related physiological and pathological processes in the body [1].

References:

1. Endo, Satoshi, Matsunaga, Toshiyuki, Hara, Akira. 2019. Mouse Akr1cl gene product is a prostaglandin D2 11-ketoreductase with strict substrate specificity. In Archives of biochemistry and biophysics, 674, 108096. doi:10.1016/j.abb.2019.108096. https://pubmed.ncbi.nlm.nih.gov/31479646/