title: Generation of a Tlx1(CreER-Venus) knock-in mouse strain for the study of spleen development.
abstract: The spleen is a lymphoid organ that serves as a unique niche for immune reactions, extramedullary hematopoiesis, and the removal of aged erythrocytes from the circulation. While much is known about the immunological functions of the spleen, the mechanisms governing the development and organization of its stromal microenvironment remain poorly understood. Here we report the generation and analysis of a Tlx1(Cre) (ER) (-Venus) knock-in mouse strain engineered to simultaneously express tamoxifen-inducible CreER(T2) and Venus fluorescent protein under the control of regulatory elements of the Tlx1 gene, which encodes a transcription factor essential for spleen development. We demonstrated that Venus as well as CreER expression recapitulates endogenous Tlx1 transcription within the spleen microenvironment. When Tlx1(Cre) (ER) (-Venus) mice were crossed with the Cre-inducible reporter strain, Tlx1-expressing cells as well as their descendants were specifically labeled following tamoxifen administration. We also showed by cell lineage tracing that asplenia caused by Tlx1 deficiency is attributable to altered contribution of mesenchymal cells in the spleen anlage to the pancreatic mesenchyme. Thus, Tlx1(Cre) (ER) (-Venus) mice represent a new tool for lineage tracing and conditional gene manipulation of spleen mesenchymal cells, essential approaches for understanding the molecular mechanisms of spleen development.
authors.affiliation: Division of Development and Aging, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakahara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawai
authors.forename: Akihisa
authors.initials: A
authors.lastname: Oda
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishimura
authors.forename: Akikazu
authors.initials: A
authors.lastname: Murakami
authors.forename: Takachika
authors.initials: T
authors.lastname: Azuma
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kaifu
authors.forename: Ryo
authors.initials: R
authors.lastname: Goitsuka
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D019070:Cell Lineage / Q000502:physiology; D003433:Crosses, Genetic; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D055879:Gene Knock-In Techniques / Q000379:methods*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D019426:Integrases / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D009024:Morphogenesis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000196:embryology*; D013629:Tamoxifen
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; C487378:Tlx1 protein, mouse; C054562:yellow fluorescent protein, Bacteria; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases
keywords: Tlx1; Venus; lineage tracing; mouse; spleen; tamoxifen-inducible Cre