Defective Mammary Epithelial Outgrowth in Transgenic EKAREV–NLS
Mice: Correction via Estrogen Supplementation and Genetic
Background Modification

J 2025

Defective Mammary Epithelial Outgrowth in Transgenic EKAREV–NLS Mice: Correction via Estrogen Supplementation and Genetic Background Modification

BREZAK, Matea a Zuzana SUMBALOVÁ KOLEDOVÁ

Základní údaje

Originální název

Defective Mammary Epithelial Outgrowth in Transgenic EKAREV–NLS Mice: Correction via Estrogen Supplementation and Genetic Background Modification

Autoři

BREZAK, Matea a Zuzana SUMBALOVÁ KOLEDOVÁ

Vydání

JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA, NEW YORK, SPRINGER/PLENUM PUBLISHERS, 2025, 1083-3021

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10605 Developmental biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.600 v roce 2024

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/25:00140660

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

EKAREV–NLS mouse; Estradiol supplementation; ERK signaling; Biosensor; Mammary epithelium; Genetic background; Hormonal imbalance

Štítky

14110517, CF CELLIM, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 7. 3. 2026 14:45, Mgr. Eva Dubská

Anotace

V originále

Fluorescent biosensors offer a powerful tool for tracking and quantifying protein activity in living systems with high temporospatial resolution. However, the expression of genetically encoded fluorescent proteins can interfere with endogenous signaling pathways, potentially leading to developmental and physiological abnormalities. The EKAREV-NLS mouse model, which carries a FRET-based biosensor for monitoring extracellular signal-regulated kinase (ERK) activity, has been widely utilized both in vivo and in vitro across various cell types and organs. In this study, we report a significant defect in mammary epithelial development in EKAREV-NLS C57BL/6J female mice. Our findings reveal that these mice exhibit severely impaired mammary epithelial outgrowth, linked to systemic defects including disrupted estrous cycling, impaired ovarian follicle maturation, anovulation, and reduced reproductive fitness. Notably, estrogen supplementation was sufficient to enhance mammary epithelial growth in the EKAREV-NLS C57BL/6J females. Furthermore, outcrossing to the ICR genetic background fully restored normal mammary epithelial outgrowth, indicating that the observed phenotype is dependent on genetic background. We also confirmed the functional performance of the biosensor in hormone-supplemented and outcrossed tissues through time-lapse imaging of primary mammary epithelial cells. Our results underscore the critical need for thorough characterization of biosensor-carrying models before their application in specific research contexts. Additionally, this work highlights the influence of hormonal and genetic factors on mammary gland development and emphasizes the importance of careful consideration when selecting biosensor strains for mammary studies.

Návaznosti

MUNI/A/1301/2022, interní kód MU

Název: Zdroje pro tkáňové inženýrství 13

Investor: Masarykova univerzita, Zdroje pro tkáňové inženýrství 13

MUNI/G/1775/2020, interní kód MU

Název: ERK signaling code of epithelial morphogenesis and cancer

Investor: Masarykova univerzita, ERK signaling code of epithelial morphogenesis and cancer, INTERDISCIPLINARY - Mezioborové výzkumné projekty

90250, velká výzkumná infrastruktura

Název: Czech-BioImaging III

Citovat

BREZAK, Matea a Zuzana SUMBALOVÁ KOLEDOVÁ. Defective Mammary Epithelial Outgrowth in Transgenic EKAREV–NLS Mice: Correction via Estrogen Supplementation and Genetic Background Modification. JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA. NEW YORK: SPRINGER/PLENUM PUBLISHERS, 2025, roč. 30, č. 1, s. 1-15. ISSN 1083-3021. Dostupné z: https://doi.org/10.1007/s10911-025-09574-8.

@article{2476577,
   author = {Brezak, Matea and Sumbalová Koledová, Zuzana},
   article_location = {NEW YORK},
   article_number = {1},
   doi = {https://doi.org/10.1007/s10911-025-09574-8},
   keywords = {EKAREV–NLS mouse; Estradiol supplementation; ERK signaling; Biosensor; Mammary epithelium; Genetic background; Hormonal imbalance},
   language = {eng},
   issn = {1083-3021},
   journal = {JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA},
   title = {Defective Mammary Epithelial Outgrowth in Transgenic EKAREV–NLS Mice: Correction via Estrogen Supplementation and Genetic Background Modification},
   url = {https://link.springer.com/article/10.1007/s10911-025-09574-8},
   volume = {30},
   year = {2025}
}

TY  - JOUR
ID  - 2476577
AU  - Brezak, Matea - Sumbalová Koledová, Zuzana
PY  - 2025
TI  - Defective Mammary Epithelial Outgrowth in Transgenic EKAREV–NLS Mice: Correction via Estrogen Supplementation and Genetic Background Modification
JF  - JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
VL  - 30
IS  - 1
SP  - 1-15
EP  - 1-15
PB  - SPRINGER/PLENUM PUBLISHERS
SN  - 10833021
KW  - EKAREV–NLS mouse
KW  - Estradiol supplementation
KW  - ERK signaling
KW  - Biosensor
KW  - Mammary epithelium
KW  - Genetic background
KW  - Hormonal imbalance
UR  - https://link.springer.com/article/10.1007/s10911-025-09574-8
N2  - Fluorescent biosensors offer a powerful tool for tracking and quantifying protein activity in living systems with high temporospatial resolution. However, the expression of genetically encoded fluorescent proteins can interfere with endogenous signaling pathways, potentially leading to developmental and physiological abnormalities. The EKAREV-NLS mouse model, which carries a FRET-based biosensor for monitoring extracellular signal-regulated kinase (ERK) activity, has been widely utilized both in vivo and in vitro across various cell types and organs. In this study, we report a significant defect in mammary epithelial development in EKAREV-NLS C57BL/6J female mice. Our findings reveal that these mice exhibit severely impaired mammary epithelial outgrowth, linked to systemic defects including disrupted estrous cycling, impaired ovarian follicle maturation, anovulation, and reduced reproductive fitness. Notably, estrogen supplementation was sufficient to enhance mammary epithelial growth in the EKAREV-NLS C57BL/6J females. Furthermore, outcrossing to the ICR genetic background fully restored normal mammary epithelial outgrowth, indicating that the observed phenotype is dependent on genetic background. We also confirmed the functional performance of the biosensor in hormone-supplemented and outcrossed tissues through time-lapse imaging of primary mammary epithelial cells. Our results underscore the critical need for thorough characterization of biosensor-carrying models before their application in specific research contexts. Additionally, this work highlights the influence of hormonal and genetic factors on mammary gland development and emphasizes the importance of careful consideration when selecting biosensor strains for mammary studies.
ER  -

BREZAK, Matea a Zuzana SUMBALOVÁ KOLEDOVÁ. Defective Mammary Epithelial Outgrowth in Transgenic EKAREV–NLS Mice: Correction via Estrogen Supplementation and Genetic Background Modification. \textit{JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA}. NEW YORK: SPRINGER/PLENUM PUBLISHERS, 2025, roč.~30, č.~1, s.~1-15. ISSN~1083-3021. Dostupné z: https://doi.org/10.1007/s10911-025-09574-8.

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