Rayane Dennaoui Rayane Dennaoui Madison N. Wicker Madison N. Wicker Carson Moen Carson Moen Michaela Schlederer Michaela Schlederer Kerry Vistisen Kerry Vistisen Aleata A. Triplett Aleata A. Triplett Thomas Rülicke Thomas Rülicke Hallgeir Rui Hallgeir Rui Lukas Kenner Lukas Kenner Emilio Casanova Emilio Casanova Kay-Uwe Wagner Kay-Uwe Wagner Elsevier 2026 Janus kinases 1 and 2 and STAT transcription factors are critical signaling nodes for numerous growth factors. In the mammary gland, JAK2 and STAT5a/b are essential for alveolar cell differentiation and lactation, but little is known about the cooperative roles of JAKs and STATs before pregnancy. We examined female mice conditionally deficient in JAK1/2 and discovered that both kinases jointly regulate epithelial cell proliferation and ductal morphogenesis. To assess the role of downstream STATs, we generated genetic models co-deficient in STAT3/5a/5b with or without STAT1 or JAK1. Although loss of STAT3/5a/5b leads to a JAK1-dependent upregulation of STAT1, the formation of mammary ducts is unaffected by the lack of expression and activation of all seven STAT proteins. Additionally, STAT deficiency impairs the cytokine-induced autophosphorylation of JAK1/2. These findings suggest that mammary duct development is orchestrated by STAT-independent signaling mechanisms of JAK1 and JAK2, potentially beyond their roles as tyrosine kinases. PDFDocument eng 2026-07-08T10:01:40.108651187Z 2026 Signal Transduction Janus Tyrosine Kinases KAK1 JAK2 STAT Proteins Gene Targeting Conditional Knockout Mammary Gland Developement Protein-tyrosine Kinase Morphogenesis Growth And Development Female DNA-binding Proteins Cre Recombinase 15433229 b application/pdf http://creativecommons.org/licenses/by-nc/4.0/