Identification of two new members of the mouse prolactin gene family.

The prolactin (PRL) family consists of a collection of genes expressed in the uterus, placenta, and anterior pituitary. These cytokines/hormones participate in the control of maternal-fetal adaptations to pregnancy. In this report, we establish the presence of two new members of the mouse PRL family. Novel expressed sequence tags (ESTs) with significant homology to PRL were isolated from embryonic, ectoplacental cone, and placental cDNA libraries. The cDNAs were sequenced and compared to other members of the PRL family. The two new cDNAs were assigned to the PRL family based on sequence homology and were referred to as PRL-like protein-F (PLP-F) and PRL-like protein-G (PLP-G). PLP-F cDNA encodes for a predicted 267 amino acid protein containing a 30 amino acid signal peptide and three putative N-linked glycosylation sites. PLP-G cDNA encodes for a predicted 266 amino acid protein containing a 30 amino acid signal peptide and six putative N-linked glycosylation sites. Sequence alignments of these proteins with other members of the PRL family suggest some unique features. Both sequences contain an extra amino acid segment located between exons two and three of the prototypical PRL gene and a nine amino acid carboxy terminal extension. PLP-F contained an additional 15 amino acid region situated between exons four and five of the prototypical PRL gene. Both PLP-F and PLP-G mRNAs were expressed in the placenta but not in other tissues (uterus, brain, thymus, heart, lung, diaphragm, liver, kidney, and ovary). In summary, the two newly identified members share approximately 50% amino acid sequence identity, are specifically expressed in the placenta, and represent a new subfamily within the PRL family.