title: Inducible knockout of Twist1 in young and adult mice prolongs hair growth cycle and has mild effects on general health, supporting Twist1 as a preferential cancer target.
abstract: Twist1 promotes epithelial-mesenchymal transition, invasion, metastasis, stemness, and chemotherapy resistance in cancer cells and thus is a potential target for cancer therapy. However, Twist1-null mice are embryonic lethal, and people with one Twist1 germline mutant allele develop Saethre-Chotzen syndrome; it is questionable whether Twist1 can be targeted in patients without severe adverse effects. We found that Twist1 is expressed in several tissues, including fibroblasts of the mammary glands and dermal papilla cells of the hair follicles. We developed a tamoxifen-inducible Twist1 knockout mouse model; Twist1 knockout in 6-week-old female mice did not affect mammary gland morphogenesis and function during pregnancy and lactation. In both males and females, the knockout did not influence body weight gain, heart rate, or total lean and fat components. The knockout also did not alter blood pressure in males, although it slightly reduced blood pressure in females. Although Twist1 is not cyclically expressed in dermal papilla cells, knockout of Twist1 at postnatal day 13 (when hair follicles have developed) drastically extended the anagen phase and accelerated hair growth. These results indicate that Twist1 is not essential for maintaining an overall healthy condition in young and adult mice and that loss of function facilitates hair growth in adulthood, supporting Twist1 as a preferential target for cancer therapy.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas; Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas; Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas.
authors.forename: Yixiang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Lan
authors.initials: L
authors.lastname: Liao
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Niya
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Theissen
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Liao
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Hoang
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: Department of Molecular and Cellular Biochemistry, Ohio State University Wexner Medical Center, Columbus, Ohio.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ludwig
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Jarrod D
authors.initials: JD
authors.lastname: Martinez
authors.affiliation: Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas; Institute for Cancer Medicine, Luzhou Medical College, Sichuan, China. Electronic address: jxu@bcm.edu.
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D005260:Female; D018859:Hair Follicle / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D006262:Health; D008297:Male; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D009369:Neoplasms / Q000378:metabolism*; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D009928:Organ Specificity; D051879:Twist-Related Protein 1 / Q000172:deficiency / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D051879:Twist-Related Protein 1; C067250:Twist1 protein, mouse
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