These mice contain a deleted segment of Chromosome 21 and are useful in studies of Down syndrome.
Roger H Reeves, Johns Hopkins University School of Medicine
These mice are monosomic for the mouse chromosome segment orthologous to the human chromosome 21 Down syndrome critical region (DSCR). The deleted segment contains mouse orthologs of 33 conserved and minimally conserved genes in the human DSCR. The borders of the deletion are defined by the carbonyl reductase 1 (Cbr1) gene and a site adjacent to the myxovirus (influenza virus) resistance 2 (Mx2) locus. Monosomic mice are viable, fertile and are significantly smaller than wildtype (euploid) littermates from birth to adulthood. This mouse may be useful in studies of Down syndrome and further exploring the ploidy of the DSCR segment of mouse Chr 16.
A targeting vector containing a 3' portion of a neomycin resistance gene, a loxP site, and a hygromycin resistance gene at the (Cbr1) locus at the proximal end of the DSCR on MMU16 was electroporated into 129S6/SvEv-derived MC1 embryonic stem (ES) cells. Correctly targeted ES cells were then electroporated with a second targeting vector designed to orient a puromycin resistance gene, a loxP site, and a 5' portion of a neomycin resistance gene adjacent to the (Mx2) locus at the distal end of MMU16. Next, a CAGGS-cre expression vector was electroporated into ES cells harboring both targeted mutations. In ES cells where each construct inserted in trans on homologous chromosomes, recombination between the loxP sites resulted in mice with a duplication of the MMU16 region between the loxP sites on one homologous chromosome and interstitial deletion of the MMU16 region between the loxP sites on the other homologous chromosome. Heterozygous ES cells were injected into blastocysts and then transferred to surrogate mothers. F1 progeny of chimeric mice were bred to (C57BL/6J x C3H/HeJ)Fn to produce mice with segmental monosomy of MMU16 (Stock# 5654 -Del(16Cbr1-ORF9)1Rhr) or segmental trisomy (see Stock# 5383 -Dp(16Cbr1-ORF9)1Rhr). Monosomic mice were crossed with (C57BL/6J x C3H/HeJ)F1 for 4 generationsbefore arriving at The Jackson Laboratory. Upon arrival, this mutant strain has been maintained by breeding with B6C3F1/J.
|Allele Name||deletion, chr 16, R H Reeves 1|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Del1Rhr; Ms1Rhr|
|Gene Symbol and Name||Del(16Cbr1-Fam3b)1Rhr, deletion, Chr16, R H Reeves 1|
|Strain of Origin||129S6/SvEvTac|
|General Note||A line of mice with segmental monosomy for Chr 16 was derived from descendants of the chimeric founder.|
|Molecular Note||Deletion of a 3.9 Mb segment of Chr 16 was engineered by cre-mediated recombination between single loxP sites inserted into homologous chromosomes. This deleted segment contains mouse orthologs of 33 conserved and minimally conserved genes in the human Down syndrome critical region.|
|Mutations Made By|| |
Roger Reeves, Johns Hopkins University School of Medicine
When maintaining a live colony, monosomic mice are bred to wildtype B6C3F1/J. Loss of reproductive function has been observed following backcross to C57BL/6J after only 2 generations. C57BL/6 is not recommended for use in breeding this strain.
When using the Ms1Rhr mouse strain in a publication, please cite the originating article(s) and include JAX stock #005654 in your Materials and Methods section.