STOCK Muc1^tm1Gend/J

Stock number: 035496
Product name: Muc1^KO
Strain synonyms: Muc1^lacZ
Research areas: Cancer Research, Research Tools

Description

Muc1 knock-out mice lack exon 1 of the mucin 1, transmembrane locus. Knock-out mice on the A/J genetic background exhibit increased numbers of lung tumors in the NNK-induced tumor model. These mice may be useful in studying lung cancer and cell proliferation.

Detailed description

The Muc1 gene encodes a tumor antigen which facilitates carcinogen-induced EGFR agtivation and is highly expressed in a number of cancer types.

The Muc1 knock-out allele (Muc1^KO, also called Muc1^lacZ) has a lacZ reporter and PGK-neo cassette replacing exon 1 of the Muc1 gene. A lack of normal Muc1 protein was indicated by immunohistochemical analysis of secretory epithelial tissue obtained from homozygous mutant mice.

On the present A/J genetic background, Muc1^KO homozygous mice exhibited an increase in the number of lung tumors in the 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced A/J mouse lung tumor model, when examined at both 30 and 45 weeks after NNK administration. Muc1^KO mice also exhibited a concomitant increase in EGFR ligand epiregulin (EREG) expression in both normal and tumor tissues of the lungs as determined by western blot analysis (Xu et al., 2017). Otherwise, homozygous mice are viable and fertile with no reported reproductive deficiency.
Mice heterozygous for the Muc1^KO allele are viable and fertile with normal breeding, and have no gross physical or behavioral abnormalities.

On a congenic C57BL/6J background, homozygous Muc1 null mice exhibit reduced growth rate of polyoma middle T antigen (MMTV-PyVT)-induced breast tumors. Specifically, by 104 days, Muc1^KO mice has significantly smaller mammary tumors than wildtype controls, though no difference was observed in the number of animals which developed tumors or in the rate of metastasis to the lungs (Spicer et al., 1995).

Although designed to have beta-galactoside directed by the endogenous Muc1 promoter, the original publication reported that the expression of the lacZ reporter did not recapitulate endogenous MUC1 expression patter in embryos and adult mice (Spicer et al., 1995).

Development

The Muc1 knock-in/knock-out allele (Muc1^KO, also called Muc1^lacZ) was created in the laboratory of Dr. Sandra Gendler (Mayo Clinic). First, a targeting vector was designed to replace exon 1 of the mucin 1, transmembrane locus (Muc1) on chromosome 3 with a lacZ cassette followed by an SV40 poly(A), and a PGK-neo cassette. The construct was electroporated into 129P2/OlaHsd-derived GK129 ES cells. Correctly targeted ES cell were then microinjected into recipient blastocysts. Chimeric progeny were crossed to C57BL/6J mice (Stock No. 000664) for germline transmission. The resulting Muc1^KO colony was then backcrossed to A/J mice (Stock No. 000646) for at least 10 generations prior to sending males to The Jackson Laboratory Repository in 2020. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes. Attempted recoveries using A/J oocytes were not productive.

Allele

Symbol: Muc1^tm1Gend
Name: targeted mutation 1, Sandra J Gendler
MGI accession ID: MGI:2447730
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Muc-1-; Muc1-
Marker symbol: Muc1
Marker name: mucin 1, transmembrane
Marker synonyms: ADMCKD; ADMCKD1; ADTKD2; CA 15-3; Ca15-3; CD227; EMA; H23AG; KL-6; MAM6; MCD; MCKD; MCKD1; MUC-1; MUC-1/SEC; MUC-1/X; MUC1/ZD; PEM; PEMT; PUM
Chromosome: 3
Strain of origin: 129P2/OlaHsd
Molecular note: A lacZ-neo construct was inserted in frame into exon 1, placing the reporter under the control of the endogenous promoter. Transcript was undetected by Northern blot analysis of homozygous mutant mice. A lack of normal protein was indicated by immunohistochemical analysis of secretory epithelial tissue obtained from homozygous mutant mice. The authors reported that the expression of lacZ did not recapitulate endogenous expression.