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A mouse model engineered to conditionally express the progesterone receptor-B isoform.


ABSTRACT: Using a Rosa26 gene targeting strategy in mouse embryonic stem cells, we have generated a new transgenic mouse (Pgr-B LSL ), which is designed to conditionally express the epitope-tagged mouse progesterone receptor-B (PGR-B) isoform when crossed with a specific cre driver mouse. To functionally validate this transgenic mouse, we crossed the Pgr-B LSL mouse with the MMTV-CREA transgenic mouse to create the MMTV-CREA/Pgr-B LSL bigenic (termed PR-B:OE to denote PGR-B overexpressor). As expected, transgene-derived PGR-B protein was specifically targeted to the virgin mammary gland epithelium. At a functional level, the PR-B:OE bigenic exhibited abnormal mammary morphogenesis-dilated epithelial ducts, precocious alveologenesis and lateral side-branching, along with a prominent proliferative signature-that resulted in pregnant PR-B:OE mice unable to exhibit mammary gland terminal differentiation at parturition. Because of this developmental failure, the PR-B:OE mammary gland was incapable of producing milk resulting in early neonatal death of otherwise healthy litters. This first line of analysis demonstrates the utility of the Pgr-B LSL mouse to examine the role of the PGR-B isoform in different physiologic and pathophysiologic systems that are responsive to progesterone.

SUBMITTER: Hai L 

PROVIDER: S-EPMC6141023 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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A mouse model engineered to conditionally express the progesterone receptor-B isoform.

Hai Lan L   Szwarc Maria M MM   Wetendorf Margeaux M   Wu San-Pin SP   Peavey Mary C MC   Grimm Sandra L SL   Edwards Dean P DP   DeMayo Francesco J FJ   Lydon John P JP  

Genesis (New York, N.Y. : 2000) 20180810 8


Using a Rosa26 gene targeting strategy in mouse embryonic stem cells, we have generated a new transgenic mouse (Pgr-B <sup>LSL</sup> ), which is designed to conditionally express the epitope-tagged mouse progesterone receptor-B (PGR-B) isoform when crossed with a specific cre driver mouse. To functionally validate this transgenic mouse, we crossed the Pgr-B <sup>LSL</sup> mouse with the MMTV-CREA transgenic mouse to create the MMTV-CREA/Pgr-B <sup>LSL</sup> bigenic (termed PR-B:OE to denote PGR-  ...[more]

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