title: The Justy mutant mouse strain produces a spontaneous murine model of salivary gland cancer with myoepithelial and basal cell differentiation.
abstract: We previously identified a novel mutant mouse strain on the C3HeB/FeJ background named Justy. This strain bears a recessive mutation in the Gon4l gene that greatly reduces expression of the encoded protein, a nuclear factor implicated in transcriptional regulation. Here, we report that Justy mutant mice aged 6 months or older spontaneously developed carcinomas with myoepithelial and basaloid differentiation in salivary glands with an incidence of ∼25%. Tumors developed proximate to submandibular glands and to a lesser extent in the sublingual and parotid glands. Histologically, tumors often had central cavitary lesions filled with necrotic debris that were lined by tumor cells, and had spindle and epithelioid cell differentiation with lesser basaloid to clear cell features. Tumor tissue often had variable evidence of a high mitotic rate, pleomorphism, and invasion into adjacent salivary glands. Neoplastic cells had diffuse immunoreactivity for pancytokeratin (AE1/AE3) and p63. Although CK5/6 immunostaining was seen in the much of the tumor cells, it was often lacking in pleomorphic areas. Tumor cells lacked immunoreactivity for alpha-smooth muscle actin, S100, c-Kit, and glial fibrillary acid protein. In addition, tumors had immunoreactivity for phosphorylated and total epidermal growth factor receptor, suggesting that EGFR signaling may participate in growth regulation of these tumors. These findings indicate that the salivary gland carcinomas occur spontaneously in Justy mice, and that these tumors may offer a valuable model for study of EGFR regulation. In combination, our data suggest that Justy mice warrant further investigation for use as a mouse model for human salivary gland neoplasia.
authors.affiliation: Department of Pathology, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Andrean L
authors.initials: AL
authors.lastname: Simons
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Katherine N
authors.initials: KN
authors.lastname: Gibson-Corley
authors.forename: Robert A
authors.initials: RA
authors.lastname: Robinson
authors.forename: David K
authors.initials: DK
authors.lastname: Meyerholz
authors.forename: John D
authors.initials: JD
authors.lastname: Colgan
mesh_terms: D000818:Animals; D002280:Basal Cell Carcinoma / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D007150:Immunohistochemistry; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D009208:Myoepithelioma / Q000473:pathology*; D009374:Neoplasms, Experimental; D009687:Nuclear Proteins / Q000235:genetics*; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C582616:Gon4l protein, mouse; D009687:Nuclear Proteins