Transcriptomics

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The butyrophilin 1a1 knock-out mouse revisited: Ablation of Btn1a1 leads to concurrent cell death and renewal in the mammary epithelium during lactation


ABSTRACT: Purpose: To assess global changes to the levels of mRNA and protein in butyrophilin-null mice (Btn1a1-/-), which were previously shown to be defective in regulated milk-lipid secretion in the lactating mammary gland. Methods: mRNA profiles of wild-type (WT) and Btn1a1-/-mice were generated by mRNA/cDNA library preparation (Illumina), qPCR quantitation, cluster generation and pair-end deep sequencing (Illumina HiSeq 4000 sequencer) using an Illumina HiSeq SBS kit. Changes in mRNA levels (null/WT ≥ ± 2-fold; adjusted p ≤ 0.05) were assesed by GSEA and IPA analysis and compared with a proteomic analysis of the same sample set.. Results: Samples had 95-167 million pass filter reads (92% above Q30). Mapping of all samples was > 97% (mm10 reference genome). Significant changes in mRNA amounts accounted for 1.4% of 11,834 transcipts (113 up and 53 down regulated). Only 10 mRNA/protein pairs were significantly upregulated and one (Btn1a1) downregulated. Pathways and networks associated with inflammation, apoptosis and the cell cycle were upregulated and lipid synthesis and metabolism were downregulated. Biochemical and histochemical analysis confirmed that lactation is maintained in null animals, in the face of significant apoptosis, by the continual regeneration of secretory epithelial cells. Cell death proceeded through several pathways including activation of caspases 8 and 3 and not by the lysosomal lysis pathway predominant in WT cells Conclusions: Ablation of Btn1a1 has multiple effects on milk-secreting mammary cells, including disruption of lipid secretion, increased cell damage and death. Lactation is maintained by continuous regeneration of the epithelium. Expression of functional Btn1a1 is essential for the maintainance of terminally differentiated mammary cells and optimal milk production throughout lactation.

ORGANISM(S): Mus musculus

PROVIDER: GSE182075 | GEO | 2021/09/20

REPOSITORIES: GEO

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