title: The impact of sperm-expressed transcription factors on fate-mapping models.
abstract: Genetic lineage tracing has been used extensively in developmental biology. Many transcription factors expressed in sperm may induce Cre-mediated loxP recombination during early zygote development. In this study, we investigated the effect of sperm-expressed Cre on cell type-specific Cre-mediated loxP recombination in fate-mapping models of Tbx18+ progenitor cells. We found the recombination frequency in a reverse mating (RM) lineage was inconsistent with a normal Mendelian distribution. However, the recombination frequency in a positive mating (PM) lineage agreed with a Mendelian distribution. In the PM lineage, LacZ and EYFP were expressed in specific locations, such as the limb buds, heart, and hair follicles. Therefore, the reporter genes accurately and reliably traced cell differentiation in the PM lineage. In contrast, EYFP and LacZ were expressed throughout the embryo in the RM lineage. Thus, the reporter genes did not trace cell differentiation specifically in the RM lineage. Furthermore, Tbx18 mRNA and protein were expressed in the testicles of male mice, but almost no Tbx18 expression was detected in the ovaries of female mice. Similarly, reporter genes and Tbx18 were coexpressed in the seminiferous tubules and sperm cells of testicles. These results revealed that Cre-loxP-mediated pre-recombination in zygotes is due to Tbx18 expressed in testicle sperm cells when Cre is transmitted paternally. Our results indicate that Cre-mediated specific recombination in fate-mapping models of sperm-expressed genes may be influenced by the paternal origin of Cre. Therefore, a careful experimental design is critical when using the Cre-loxP system to trace spatial, temporal or tissue-specific fates.
authors.affiliation: Departments of NephrologyCardiologySecond Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Departments of NephrologyCardiologySecond Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Du
authors.affiliation: Departments of NephrologyCardiologySecond Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Qin
authors.affiliation: Departments of NephrologyCardiologySecond Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Li
authors.affiliation: Departments of NephrologyCardiologySecond Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Songbai
authors.initials: S
authors.lastname: Deng
authors.affiliation: Departments of NephrologyCardiologySecond Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Departments of NephrologyCardiologySecond Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Departments of NephrologyCardiologySecond Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China qshe98@hotmail.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: She
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D005260:Female; D017930:Genes, Reporter; D018859:Hair Follicle / Q000201:enzymology / Q000378:metabolism; D006321:Heart / Q000196:embryology; D018878:Limb Buds / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D011995:Recombination, Genetic; D013094:Spermatozoa / Q000378:metabolism*; D013234:Stem Cells; D020825:T-Box Domain Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D020825:T-Box Domain Proteins; C420983:Tbx18 protein, mouse; D014157:Transcription Factors