phaidra.vetmeduni.ac.at o:5279 DOI 10.1016/j.celrep.2025.116703 STAT-independent functions of Janus kinases 1 and 2 are obligatory for the postnatal development of mammary epithelial ducts 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. eng 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 2026-07-08T10:01:40.433Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Dennaoui;Rayane; FN:Rayane Dennaoui END:VCARD BEGIN:VCARD VERSION:3.0 N:Wicker;Madison N.; FN:Madison N. Wicker END:VCARD BEGIN:VCARD VERSION:3.0 N:Moen;Carson; FN:Carson Moen END:VCARD BEGIN:VCARD VERSION:3.0 N:Schlederer;Michaela; FN:Michaela Schlederer END:VCARD BEGIN:VCARD VERSION:3.0 N:Vistisen;Kerry; FN:Kerry Vistisen END:VCARD BEGIN:VCARD VERSION:3.0 N:Triplett;Aleata A.; FN:Aleata A. Triplett END:VCARD BEGIN:VCARD VERSION:3.0 N:Rülicke;Thomas; FN:Thomas Rülicke X-ORCID:https://orcid.org/0000-0002-2121-9496 END:VCARD BEGIN:VCARD VERSION:3.0 N:Rui;Hallgeir; FN:Hallgeir Rui END:VCARD BEGIN:VCARD VERSION:3.0 N:Kenner;Lukas; FN:Lukas Kenner X-ORCID:https://orcid.org/0000-0003-2184-1338 END:VCARD BEGIN:VCARD VERSION:3.0 N:Casanova;Emilio; FN:Emilio Casanova END:VCARD BEGIN:VCARD VERSION:3.0 N:Wagner;Kay-Uwe; FN:Kay-Uwe Wagner X-ORCID:https://orcid.org/0000-0002-5081-0226 END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by-nc/4.0 application/pdf 15433229 https://phaidra.vetmeduni.ac.at/o:5279 https://phaidra.vetmeduni.ac.at/api/object/o:5279/thumbnail LOMv1.0 discipline