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Mammary gland development is delayed in mice deficient for aminopeptidase N

Abstract

Development of the mammary gland requires the coordinated action of proteolytic enzymes during two phases of remodelling. Firstly, new ducts and side-branches thereof need to be established during pregnancy to generate an extensive ductal tree allowing the secretion and transport of milk. A second wave of remodelling occurs during mammary involution after weaning. We have analysed the role of the cell surface protease aminopeptidase N (Anpep, APN, CD13) during these processes using Anpep deficient and Anpep over-expressing mice. We find that APN deficiency significantly delays mammary gland morphogenesis during gestation. The defect is characterised by a reduction in alveolar buds and duct branching at mid-pregnancy. Conversely over-expression of Anpep leads to accelerated ductal development. This indicates that Anpep plays a critical role in the proteolytic remodelling of mammary tissue during adult mammary development.

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Abbreviations

APN, Anpep:

Aminopeptidase N

BAC:

Bacterial artificial chromosome

ES cells:

Embryonic stem cells

HRP:

Horse radish peroxidase

MMP:

Matrix metallo-proteinase

PCR:

Polymerase chain reaction

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Acknowledgments

The work was supported by the EU framework VI project grant (QOL-2000-00874) and the Hannah Development Fund.

Author information

Correspondence to Andreas F. Kolb.

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Kolb, A.F., Sorrell, D., Lassnig, C. et al. Mammary gland development is delayed in mice deficient for aminopeptidase N. Transgenic Res 22, 425–434 (2013). https://doi.org/10.1007/s11248-012-9654-7

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Keywords

  • Mammary gland
  • Protease
  • Gene locus
  • Homologous recombination
  • Development