This targeted mutation of the gremlin 1(Grem1) gene displays homozygous postnatal lethality, absent kidneys, and abnormal limbs and may be useful in the studies of limb patterning and kidney development.
Richard Harland, University of California, Berkeley
Mice that are homozygous for the targeted mutation lack kidneys and die within 48 hours of birth. These mice exhibit a single bone in both the forelimb and hindlimb zeuogopod, missing digits and abnormal maintenance of interdigital tissue. Beta galactosidase expression in the embryonic limbs, somites and flank is consistent with the expression of gremlin 1. This mutant mouse strain may be useful in studies of limb patterning and kidney development.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector containing the LacZ gene fused to the first 5 residues of gremlin 1 and an FRG-flanked PGK neomycin resistance cassette was used to replace an open reading frame . The construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6J for 8 generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Expressed Gene||lacZ, beta-galactosidase, E. coli|
|Site of Expression|
|Allele Name||targeted mutation 1, Richard M Harland|
|Allele Type||Targeted (Reporter, Null/Knockout)|
|Allele Synonym(s)||Grem1-; gremlinLacZ; ldgrm|
|Gene Symbol and Name||Grem1, gremlin 1, DAN family BMP antagonist|
|Expressed Gene||lacZ, beta-galactosidase, E. coli|
|Strain of Origin||129P2/OlaHsd|
|General Note||This mutation was determined through complementation analysis to be allelic to Grem1ld-J (J:84077).Heterozygous mutant mice were viable and fertile. Serial skeletal stains of cartilage and bone of heterozygous mutant embryos and newborn mice showed no abnormalities in limb development.|
|Molecular Note||The open reading frame, which lies on a single exon, was replaced with an in frame fusion of lacZ with the sequence encoding the first five residues followed by an frt flanked neomycin resistance cassette. The neomycin cassette can then be removed by crossing to mice expressing Flp recombinase. Mice with and without the neomycin cassette have the same phenotype. lacZ expression in heterozygous mutant mice recapitulates that of wild-type mice.|
|Mutations Made By|| |
Dr. Lisa Brunet, Univ of California at Berkeley
While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation are not viable.
When using the B6.129P2-Grem1tm1Rmh/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010949 in your Materials and Methods section.
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