title: Two new targeted alleles for the comprehensive analysis of Meis1 functions in the mouse.
abstract: Meis1 is a highly conserved transcription factor that is activated in a regionally restricted manner from early stages of development. Meis1 belongs to the three amino acid loop extension (TALE) homeodomain family. Together with Pbx1, Meis1 plays a major role as a Hox cofactor, and therefore, plays an essential role in the development of several embryonic organs and systems, including limbs, heart, blood, and vasculature. In addition, Meis1 is required for the development of Hox-free embryonic regions and interacts with non-Hox homeodomain and non-homeodomain transcription factors. During post-natal life Meis1 is involved in adult cardiomyocyte homeostasis and has been associated with pre-disposition to human neural and cardiac pathologies. Given the relevance of this transcription factor, we have developed two new Meis1 gene knockin models; a direct ECFP knockin insertion that allows the direct identification of Meis1-expressing cells in living tissues, and a CreERT2 insertion that allows the inducible genetic tracing of Meis1-expressing cells in a time-controlled manner. Importantly, these two alleles represent the first Meis1 mutations in which Meis1 protein production is completely eliminated. These newly targeted Meis1 alleles will be valuable tools to further our understanding of the role of this critical transcription factor during development and disease.
authors.affiliation: Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares, CNIC, Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: González-Lázaro
authors.forename: Alberto
authors.initials: A
authors.lastname: Roselló-Díez
authors.forename: Irene
authors.initials: I
authors.lastname: Delgado
authors.forename: Laura
authors.initials: L
authors.lastname: Carramolino
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Sanguino
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giovinazzo
authors.forename: Miguel
authors.initials: M
authors.lastname: Torres
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D055879:Gene Knock-In Techniques / Q000379:methods*; D056426:Genetic Loci; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016254:Mutagenesis, Insertional / Q000379:methods*; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype
chemical_list: D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins
keywords: ECFP reporter protein expression; Meis1 knockin; lineage tracing; tamoxifen-inducible CreERT2