PXD021249

PXD021249 is an original dataset announced via ProteomeXchange.

Title	Ablation of Btn1a1 leads to concurrent cell death and renewal in the mammary epithelium during lactation
Description	Butyrophilin 1A1 (BTN1A1) was first identified as a major integral protein of both the apical surface of mammary epithelial cells during lactation and the surface membrane surrounding lipid droplets in milk. Current evidence supports a role for BTN1A1 in the secretion of milk lipids as a membrane receptor, which forms a secretion complex with the redox enzyme, xanthine oxidoreductase (XDH). Capping of cytoplasmic lipid droplets with BTN1A1 and XDH serves to envelop the droplets with cellular membranes at the cell apex as an initial step in their subsequent release from the cell. The first evidence that BTN1A1 functions in this process was the generation of Btn1a1-/- mice, in which lipid secretion was disrupted and large unstable droplets were released into alveolar spaces with fragmented surface membranes. We have revisited this mutant mouse line using RNAseq and proteomic analysis to fully assess the consequences of ablating the Btn1a1 gene on the expression of other genes and proteins. Disruption of Btn1a1 expression led to a large build-up of Xdh (6-fold over wild-type levels) in the cytoplasm, induction of acute phase response genes and Lif-activation of STAT3 phosphorylation. At peak lactation, approx. 10% of the cells were dying, as assessed by TUNEL-analysis of nuclear DNA. Cell death appeared to proceed through expression of caspase 8 and activated caspase 3 and not via lysosomal lysis, which is the principal route for elimination of cells during mammary involution in wild-type mice. Other potential death pathways include autophagy and Slc5a8-mediated inactivation of survivin (Birc5). Milk secretion was prolonged by renewal of the secretory epithelium, as evidenced by the expression of cyclins, Fos/Jun and upregulation of Ki67 in approx. 10% of secretory cell nuclei. Thus a 21-day lactation cycle can be maintained, despite significant cell death by compensatory cell division, provided a milking stimulus is maintained. These data highlight the importance of BTN1A1 expression for the maintenance of terminally differentiated mammary epithelial cells and optimal milk production throughout lactation. From a practical standpoint, the complimentary RNAseq and proteomics data should provide a useful reference database for gene and protein expression in C57/Bl6 mice at peak lactation.
HostingRepository	PRIDE
AnnounceDate	2021-09-20
AnnouncementXML	Submission_2021-09-20_14:26:52.020.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD021249
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Lisa Jenkins
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-01 01:53:02	ID requested
⏵ 1	2021-09-20 14:26:52	announced

Dataset with its publication pending

submitter keyword: Btn1a1, butyrophilin 1a1, lactation, milk-lipid secretion

Lisa M. Jenkins
contact affiliation	National Cancer Institute, NIH Bethesda, MD 20892
contact email	lisa.jenkins@nih.gov
lab head
Lisa Jenkins
contact affiliation	National Cancer Institute, NIH
contact email	lisa.jenkins@nih.gov
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021249
     1. Label: PRIDE project
     2. Name: Ablation of Btn1a1 leads to concurrent cell death and renewal in the mammary epithelium during lactation