Complete rescue of the nude mutant phenotype by a wild-type Foxn1 transgene.
In this paper we describe the production and analysis of mice carrying a 110-kb transgene that encompasses the wild-type Foxn1 genomic locus. Mutations in Foxn1 cause the nude phenotype. We show that in the hair follicles, transgenic mice with increased Foxn1 gene dosage exhibited increased Foxn1 expression that was restricted correctly to the nascent, post-mitotic cells of the differentiating hair cortex and hair cuticle lineages. We also demonstrate for the first time that a Foxn1 transgene rescues completely both the hair follicle and the thymus defects in animals that are also homozygous for the nude mutation at the endogenous Foxn1 locus, causing the development of a full coat of hair and a normal population of peripheral blood T lymphocytes. We conclude that sufficient cis-acting regulatory information resides within this 110-kb transgene to direct reliable and appropriate tissue-specific expression of the Foxn1 gene.
Cunliffe
Vincent T
VT
Centre for Developmental Genetics, School of Medicine and Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK. v.t.cunliffe@shef.ac.uk
Furley
Andrew J W
AJ
Keenan
Deborah
D
D000818:Animals; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005260:Female; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018859:Hair Follicle / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude / Q000235:genetics* / Q000502:physiology; D008822:Mice, Transgenic / Q000235:genetics* / Q000502:physiology; D018613:Microscopy, Confocal; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D012867:Skin / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D019076:Transgenes
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; C090140:Whn protein; D004247:DNA