Foxp3 heterozygosity does not overtly affect mammary gland development during puberty or the oestrous cycle in mice
Vahid Atashgaran A B , Pallave Dasari A B , Leigh J. Hodson A B , Andreas Evdokiou A , Simon C. Barry B C and Wendy V. Ingman A B DA Discipline of Surgical Specialties, Adelaide Medical School, The Queen Elizabeth Hospital, University of Adelaide, Woodville, SA 5011, Australia.
B Robinson Research Institute, University of Adelaide, SA 5005, Australia.
C Molecular Immunology Laboratory, Discipline of Paediatrics, Adelaide Medical School, University of Adelaide, North Adelaide, SA 5006, Australia.
D Corresponding author. Email: wendy.ingman@adelaide.edu.au
Reproduction, Fertility and Development 32(8) 774-782 https://doi.org/10.1071/RD19378
Submitted: 4 October 2019 Accepted: 20 January 2020 Published: 20 April 2020
Abstract
Female mice heterozygous for a genetic mutation in transcription factor forkhead box p3 (Foxp3) spontaneously develop mammary cancers; however, the underlying mechanism is not well understood. We hypothesised that increased cancer susceptibility is associated with an underlying perturbation in mammary gland development. The role of Foxp3 in mammary ductal morphogenesis was investigated in heterozygous Foxp3Sf/+ and wildtype Foxp3+/+ mice during puberty and at specific stages of the oestrous cycle. No differences in mammary ductal branching morphogenesis, terminal end bud formation or ductal elongation were observed in pubertal Foxp3Sf/+ mice compared with Foxp3+/+ mice. During adulthood, all mice underwent normal regular oestrous cycles. No differences in epithelial branching morphology were detected in mammary glands from mice at the oestrus, metoestrus, dioestrus and pro-oestrus stages of the cycle. Furthermore, abundance of Foxp3 mRNA and protein in the mammary gland and lymph nodes was not altered in Foxp3Sf/+ mice compared with Foxp3+/+ mice. These studies suggest that Foxp3 heterozygosity does not overtly affect mammary gland development during puberty or the oestrous cycle. Further studies are required to dissect the underlying mechanisms of increased mammary cancer susceptibility in Foxp3Sf/+ heterozygous mice and the function of this transcription factor in normal mammary gland development.
Additional keywords: developmental biology, ductal epithelium, mammary gland morphogenesis, mouse model, regulatory T cells, terminal end bud.
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