title: CA125/MUC16 is dispensable for mouse development and reproduction.
abstract: Cancer antigen 125 (CA125) is a blood biomarker that is routinely used to monitor the progression of human epithelial ovarian cancer (EOC) and is encoded by MUC16, a member of the mucin gene family. The biological function of CA125/MUC16 and its potential role in EOC are poorly understood. Here we report the targeted disruption of the of the Muc16 gene in the mouse. To generate Muc16 knockout mice, 6.0 kb was deleted that included the majority of exon 3 and a portion of intron 3 and replaced with a lacZ reporter cassette. Loss of Muc16 protein expression suggests that Muc16 homozygous mutant mice are null mutants. Muc16 homozygous mutant mice are viable, fertile, and develop normally. Histological analysis shows that Muc16 homozygous mutant tissues are normal. By the age of 1 year, Muc16 homozygous mutant mice appear normal. Downregulation of transcripts from another mucin gene (Muc1) was detected in the Muc16 homozygous mutant uterus. Lack of any prominent abnormal phenotype in these Muc16 knockout mice suggests that CA125/MUC16 is not required for normal development or reproduction. These knockout mice provide a unique platform for future studies to identify the role of CA125/MUC16 in organ homeostasis and ovarian cancer.
authors.affiliation: Program in Genes and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.
authors.forename: Dong-Joo
authors.initials: DJ
authors.lastname: Cheon
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Jian Min
authors.initials: JM
authors.lastname: Deng
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lu
authors.forename: Lianchun
authors.initials: L
authors.lastname: Xiao
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Chen
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bast
authors.forename: Richard R
authors.initials: RR
authors.lastname: Behringer
mesh_terms: D000367:Age Factors; D000818:Animals; D018394:CA-125 Antigen / Q000502:physiology*; D005260:Female; D048788:Growth and Development; D006706:Homeostasis; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010051:Ovarian Neoplasms / Q000209:etiology; D010641:Phenotype; D012098:Reproduction
chemical_list: D018394:CA-125 Antigen; C534798:MUC16 protein, mouse; D008565:Membrane Proteins