The promoter and exons 1-4 of the matrix Gla protein (Mgp) gene has been disrupted in these mice. Homozygous mice develop vascular calcification involving ectopic bone formation and osteochondrogenic differentiation in multipotent cells in the vascular media and endothelium. These Mgpm1 mice may be useful for studying arterial calcification.
Kristina Bostrom, David Geffen School of Medicine at UCLA
A neo cassette replaces the promoter and exons 1-4 of the matrix Gla protein (Mgp) gene, abolishing gene expression. Homozygotes are viable but die within two months of age due to aortic rupture. Normally, MGP is present in bone, heart, kidney, lung, aorta and other vasculature, and can function as an arterial calcification inhibitor. These Mgpm1 mice develop vascular calcification involving ectopic bone formation and osteochondrogenic differentiation in multipotent cells in the vascular media and endothelium. Lack of MGP in the endothelium triggers endothelial-mesenchymal transitions, which allow the endothelial cells to contribute cells to the vascular calcification. Mgpm1 mice also exhibit abnormal calcification patterns in cartilage and the bone growth plate, which eventually leads to short stature and osteopenia. The lack of MGP also causes arteriovenous malformations (AVMs) in the lungs, kidneys and brain. The AVMs in the lungs and kidneys are associated with abnormal cell differentiation in the endothelium.
A targeting vector was designed to replace the promoter and exons 1-4 of the matrix Gla protein (Mgp) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S7/SvEvBrd-Hprtb-m2-derived AB2.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. These mice were backcrossed for at least 10 generations to C57BL/6J background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Gerard Karsenty|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||MGP-; mgpm1|
|Gene Symbol and Name||Mgp, matrix Gla protein|
|Strain of Origin||129S7/SvEvBrd-Hprtb-m2|
|General Note||Phenotypic Similarity to Human Syndrome: Singleton-Merten Syndrome in homozygous mice (J:38867)|
|Molecular Note||A neomycin resistance cassette replaced a 3.4 kb fragment of the gene containing the proximal promoter, exons 1, 2, 3, and most of 4. Northern blots of RNA from lungs of homozygous mutant mice showed no detectable transcript for the targeted protein.|
|Mutations Made By|| |
Yanfeng (Mei) Speer, University of Washington
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony, or to C57BL/6J inbred mice (Stock No. 000664). Homozygous mice survive to 2 months of age and then die due to rupture and subsequent hemorrhage of the thoracic and abdominal aorta.
When using the B6.129S7-Mgptm1Kry/KbosJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #023811 in your Materials and Methods section.