Homozygous Men1 knock-out mice exhibit embryonic lethality with defects in cranial/facial formation. Heterozygotes develop parathyroid adenomas and may be useful in applications related to the studies of multiple endocrine neoplasia type 1 (MEN1) in humans.
Francis S. Collins, NHGRI/NIH
Mice that are homozygous null for the Men1 gene die in utero at embryonic days 10.5-11.5, exhibiting delayed development often (20%) with defects in cranial/facial formation. At birth, heterozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. At nine months, ~80% of the heterozygous-null mice develop abnormalities in pancreatic islet cells, the severity of which ranges from hyperplasia to insulin-producing tumors. Parathyroid adenomas are also observed at this age. Tumor incidence is progressive, with occurrences in multiple endocrine tissues (pancreatic islets, parathyroids, thyroid, adrenal cortex, pituitary) by sixteen months of age.
A targeting vector containing a loxP-bracketed neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was inserted into intron 2 of the Men1 gene. Another loxP site was positioned within intron 8. The construct was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were bred to 129S6/SvEvTacFBR females. The progeny were heterozygous for the floxed allele (TSM/+). These heterozygous mice were bred with a ubiquitously expressing Cre mouse line (EIIa-Cre) on an FVB background. The resulting mice were heterozygous for an allele that lacked the PGK-Neo cassette and Men1 exons 3-8.
|Allele Name||targeted mutation 1.1, Judy S Crabtree|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||dN3-8; Men1-; Men1deltaN3-8; Men1deltaN3-8|
|Gene Symbol and Name||Men1, multiple endocrine neoplasia 1|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||This allele is a derivative of Men1tm1Ctre in which the neomycin cassette and exons 3-8 of the gene were removed by Cre mediated recombination by crossing mice carrying the Mentm1Ctre allele to mice expressing Cre recombinase under the control of a ubiquitous promoter.|
|Mutations Made By|| |
Judy Crabtree, Louisiana State University School of Med
Homozygotes are embryonic lethal. When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony. The coat color expected from breeding is Black, Agouti.
When using the Men1ΔN3–8 mouse strain in a publication, please cite the originating article(s) and include JAX stock #004066 in your Materials and Methods section.