Meanwhile, Muc16?/? male mice exhibited high reproductive ability, as their crossing with WT females yielded more progenies as compared to the ones crossed with WT male mice. role of mucins under various pathological conditions, information regarding the physiologically relevant functions of mucins in context Sildenafil Mesylate of the microenvironment which exists in tissue/tumor and complex interactions among different cell types remains obscure and underexplored. Therefore, the development of suitable animal models will provide an improved understanding of the consequence of dysregulation under normal and pathological conditions. Xenograft models have been helpful in validating the findings [20C24]; however, these models have several limitations including lack of competent immune system and factual microenvironment. Since recent reports have implicated the importance of mucins in Sildenafil Mesylate immune system regulation, it is critical to study the role of mucins in the context of a functional immune system [25, 26]. These shortcomings could be overcome by utilizing transgenic (Tg), knockin (KI), and knockout (KO) mouse models, collectively known as genetically engineered mouse (GEM) models. Cre-Lox and Flp-FRT recombination systems are the most commonly used approaches for the development of conditional and inducible KO and KI mouse models [27, 28]. Some of the mucin mouse models have provided crucial information about the importance of mucins Sildenafil Mesylate including their role under physiological and pathological conditions. In this review article, we intend to provide an overall picture of the currently available mucin mouse models and discuss their utility for understanding mucin function under inflammatory and malignant pathologies. 2 Comparative analysis and synteny of mouse and human mucins Mice are frequently used as a model system to study the biology of human diseases because of their small size, ease of manipulation, short generation interval, and relatively inexpensive maintenance costs. Before describing the usefulness Rabbit Polyclonal to TALL-2 of murine models to understand the function of human mucins, it is important to emphasize the homology between murine and human mucins. Table 2 summarizes different types of human mucins, their homologues in mice, and their genomic localization. Mucins consist of multiple domains (Fig. 2): sperm protein, enterokinase, and the agrin domain (SEA) involved in protein interactions; epidermal growth factor (EGF)-like domain that can act as a ligand; cysteine-rich dimerization or D domain (including D1, D2, D, D3 similar to von Willebrand (vWD) domains) for oligomerization; variable number of tandem repeats (VNTR or TRs) rich in serine (Ser), threonine (Thr), proline (Pro) (collectively known as S/T/P) for O-linked glycosylation; the hydrophobic trans-membrane (TM) domain for cell surface localization and cytoplasmic tail (CT) to facilitate signal transduction [31, 32]. The domain organization and expression pattern of mucins is largely conserved between human and mouse and is discussed below in detail. Open in a separate window Fig. 2 Representation of the prototype structure of mucins along with the characterized and putative roles of their functional domains: MBMs and SMs have a TR domain with variable numbers and lengths of the repeats. They are predominantly get O-glycosylated and separated by unique sequences. They also have few N-glycosylation sites with varying localization with different mucins. Most of the MBMs possess SEA domains with a potential cleavage site (G/SVVV), except MUC4 where GDPH (also present in MUC2 and MUC5 AC secretory mucins) is considered to be a putative site for cleavage. Mucins have varying lengths of CT (MUC4 CT is shortest with 22 amino acids), which are believed to facilitate signal transduction due to the presence of potential phosphorylation sites such as Ser, Thr, and Tyr residues. Other domains present in mucins include EGF-like motifs, nidogen and adhesion-associated NIDO and AMOP, and vWD domains. SMs are rich in cys-rich domains (D1, D2, D3, and D4), which are similar to the D domains of the vWD factor and Sildenafil Mesylate flank the TR region. These domains are important for disulfide cross-linking to allow oligomerization between the mucin molecules required for gel-forming network Table 2 Different human mucin homologues of mice and their genomic localization transmembrane, not present aMuc3 is 46.4 and 59.6 % similar to human MUC3 and MUC17,.