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Genetically engineered mucin mouse models for inflammation and cancer

  • Non-Thematic Review
  • Published:
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Abstract

Mucins are heavily O-glycosylated proteins primarily produced by glandular and ductal epithelial cells, either in membrane-tethered or secretory forms, for providing lubrication and protection from various exogenous and endogenous insults. However, recent studies have linked their aberrant overexpression with infection, inflammation, and cancer that underscores their importance in tissue homeostasis. In this review, we present current status of the existing mouse models that have been developed to gain insights into the functional role(s) of mucins under physiological and pathological conditions. Knockout mouse models for membrane-associated (Muc1 and Muc16) and secretory mucins (Muc2) have helped us to elucidate the role of mucins in providing effective and protective barrier functions against pathological threats, participation in disease progression, and improved our understanding of mucin interaction with biotic and abiotic environmental components. Emphasis is also given to available transgenic mouse models (MUC1 and MUC7), which has been exploited to understand the context-dependent regulation and therapeutic potential of human mucins during inflammation and cancer.

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Abbreviations

MUC1:

Human mucin

Muc1:

Mouse mucin

KO:

Knockout

KI:

Knockin

Tg:

Transgenic

KC:

Cre-LSL-KrasG12D

KCM:

KC mice with human MUC1 overexpression

KCKO:

KC mice with Muc1 knockout

CF:

Cystic fibrosis

SEA:

Sperm protein, enterokinase, and agrin domain

EGF-L:

Epidermal growth factor (EGF)-like domain

D domain:

Dimerization domain

TR:

Variable number of tandem repeats

Ser:

Serine

Thr:

Threonine

Pro:

Proline

TM:

Transmembrane

CT:

Cytoplasmic tail

CTCK:

Cystine knot-like domain

rCCSP:

Rat Clara cell secretory protein

vWD:

Von Willebrand

T-reg:

Regulatory T cells

WT:

Wild type

CTL:

Cytotoxic T lymphocytes

APCs:

Antigen-presenting cells

CSCs:

Cancer stem cells

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Acknowledgments

The authors on this work are supported, in part, by grants from the National Institutes of Health (TMEN U54 CA163120, EDRN UO1 CA111294, RO1 CA183459, SPORE P50 CA127297, RO1 CA78590, P20 GM103480, R21 CA155175, R21 CA156037, and RO3 CA167342).

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  1. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA

    Suhasini Joshi, Sushil Kumar, Sangeeta Bafna, Satyanarayana Rachagani, Maneesh Jain & Surinder K. Batra

  2. Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA

    Kay-Uwe Wagner, Maneesh Jain & Surinder K. Batra

  3. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA

    Kay-Uwe Wagner, Maneesh Jain & Surinder K. Batra

  4. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA

    Surinder K. Batra

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  1. Suhasini Joshi
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Joshi, S., Kumar, S., Bafna, S. et al. Genetically engineered mucin mouse models for inflammation and cancer. Cancer Metastasis Rev 34, 593–609 (2015). https://doi.org/10.1007/s10555-015-9549-1

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