ABCD4 is associated with mammary gland development in mammals

BMC Genomics. 2024 May 20;25(1):494. doi: 10.1186/s12864-024-10398-9.

Abstract

Background: Mammary gland development is a critical process in mammals, crucial for their reproductive success and offspring nourishment. However, the functional roles of key candidate genes associated with teat number, including ABCD4, VRTN, PROX2, and DLST, in this developmental process remain elusive. To address this gap in knowledge, we conducted an in-depth investigation into the dynamic expression patterns, functional implications, and regulatory networks of these candidate genes during mouse mammary gland development.

Results: In this study, the spatial and temporal patterns of key genes were characterized in mammary gland development. Using time-series single-cell data, we uncovered differences in the expression of A bcd4, Vrtn, Prox2, and Dlst in cell population of the mammary gland during embryonic and adult stages, while Vrtn was not detected in any cells. We found that only overexpression and knockdown of Abcd4 could inhibit proliferation and promote apoptosis of HC11 mammary epithelial cells, whereas Prox2 and Dlst had no significant effect on these cells. Using RNA-seq and qPCR, further analysis revealed that Abcd4 can induce widespread changes in the expression levels of genes involved in mammary gland development, such as Igfbp3, Ccl5, Tlr2, and Prlr, which were primarily associated with the MAPK, JAK-STAT, and PI3K-AKT pathways by functional enrichment.

Conclusions: These findings revealed ABCD4 as a candidate gene pivotal for regulating mammary gland development and lactation during pregnancy by influencing PRLR expression.

Keywords: ABCD4; PRLR; HC11; Mammary gland development.

MeSH terms

  • ATP-Binding Cassette Transporters* / genetics
  • ATP-Binding Cassette Transporters* / metabolism
  • Animals
  • Apoptosis / genetics
  • Cell Proliferation
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks
  • Mammary Glands, Animal* / growth & development
  • Mammary Glands, Animal* / metabolism
  • Mice
  • Signal Transduction

Substances

  • Abcd4 protein, mouse
  • ATP-Binding Cassette Transporters