Cunliffe Vincent T, Furley Andrew J W, Keenan Deborah
Centre for Developmental Genetics, School of Medicine and Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
Mamm Genome. 2002 May;13(5):245-52. doi: 10.1007/s00335-001-3079-6.
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.
在本文中,我们描述了携带一个包含野生型Foxn1基因组位点的110 kb转基因小鼠的产生和分析。Foxn1突变会导致裸鼠表型。我们发现,在毛囊中,Foxn1基因剂量增加的转基因小鼠表现出Foxn1表达增加,且这种增加正确地局限于正在分化的毛皮质和毛小皮谱系的新生、有丝分裂后细胞。我们还首次证明,一个Foxn1转基因完全挽救了在内源Foxn1位点也是裸鼠突变纯合子的动物的毛囊和胸腺缺陷,导致长出完整的毛发并发育出正常数量的外周血T淋巴细胞。我们得出结论,这110 kb转基因中存在足够的顺式作用调控信息,可指导Foxn1基因可靠且适当地进行组织特异性表达。