|The neurodevelopmental disorder Williams-Beuren Syndrome (WBS) is caused by spontaneous 1.5 Mb deletions comprising 25 genes on human chromosome 7q11.23. This mutant mouse strain carries a deletion corresponding to the distal half of the conserved syntenic region on mouse Chromosome 5G2, referred to as the distal deletion (DD).|
Type Deletion; Additional information on Mice with Chromosomal Aberrations. Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator Karl Deisseroth, Stanford University
The neurodevelopmental disorder Williams-Beuren Syndrome (WBS) is caused by spontaneous 1.5 Mb deletions comprising 25 genes on human chromosome 7q11.23. This mutant mouse strain carries a deletion corresponding to the proximal half of the conserved syntenic region on mouse Chromosome 5G2, referred to as the distal deletion (DD).
DD mice lack a genomic segment between and including the Limk1 to Trim50 genes. Crosses with animals lacking genomic sequences corresponding to the proximal portion of the WBS deletion region (see Stock No. 023885; also called PD) create double heterozygous animals with deletions representing the length of the WBS region (D/P mice). Both PD and D/P males are growth-retarded, while skulls are shortened and brains are smaller in DD and D/P. Lateral ventricle volumes are reduced, and neuronal cell density in the somatosensory cortex is increased, in PD and D/P. Motor skills are most impaired in D/P animals and their fertility is somewhat reduced. Together, these partial deletion mice replicate crucial aspects of the human disorder and serve to identify genes and gene networks contributing to the neural substrates of complex behaviours and behavioural disorders.
A genomic segment corresponding to the distal portion of the Williams-Beuren Syndrome (WBS) deletion region was excised in these mice. To create the mutation, a neomycin resistance cassette, a loxP site, the 5' portion of the Hprt minigene, and Limk1 exons 3 and 4 were introduced to intron 2 of the Limk1 locus. The 3' portion of the Hprt minigene, loxP site and puromycin resistance cassette were inserted into intron 2 of the Trim50 gene. These mutations were introduced through homologous recombination to AB2.2 129S7/SvEvBrd-Hprt1b-m2-derived embryonic stem (ES) cells. Resultant chimeric mice were crossed with Zp3-cre transgenic mice (see Stock No. 003651) to excise the genomic region flanked by loxP sites. These mice were maintained on a mixed C57BL/6J and 129 genetic background by the donating laboratory.
|Wild-type from the colony|
|Considerations for Choosing Controls|
View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
Del(5Limk1-Trim50)2Uta/+involves: 129S7/SvEvBrd * C57BL/6J
- premature death
- some female mice exhibit rectal or vaginal prolapse leading to euthanasia (MGI Ref ID J:182796)
- reproductive system phenotype
- abnormal vagina morphology
- vaginal prolapse in some female mice leading to euthanasia (MGI Ref ID J:182796)
- behavior/neurological phenotype
- abnormal social investigation
- in a partition test, mice exhibit increased social interest compared with wild-type mice (MGI Ref ID J:182796)
- abnormal startle reflex
- the percent inhibition of startle caused by the presence of a gap in the sound is increased compared to in wild-type mice (MGI Ref ID J:182796)
- decreased exploration in new environment
- in an open field test (MGI Ref ID J:182796)
- impaired contextual conditioning behavior (MGI Ref ID J:182796)
- impaired cued conditioning behavior (MGI Ref ID J:182796)
- nervous system phenotype
- *normal* nervous system phenotype
- mice exhibit normal lateral ventricle size (MGI Ref ID J:182796)
- craniofacial phenotype
- *normal* craniofacial phenotype
- mice exhibit normal teeth morphology (MGI Ref ID J:182796)
- growth/size/body phenotype
- decreased body weight
- herniated abdominal wall
- postnatal growth retardation (MGI Ref ID J:182796)
- cardiovascular system phenotype
- abnormal blood vessel physiology
- mice exhibit reduced abdominal aortic anterior wall motion compared with wild-type mice (MGI Ref ID J:182796)
- digestive/alimentary phenotype
- rectal prolapse
- in some female mice leading to euthanasia (MGI Ref ID J:182796)
- skeleton phenotype
- abnormal cranium size
- foreshortened, more so in female mice than in male mice (MGI Ref ID J:182796)
- decreased cranium width
- in the anterior and mid-portions, more so in female mice than in male mice (MGI Ref ID J:182796)View Research Applications
|Allele Name||deletion, Chr 5, Uta Francke 2|
|Allele Type||Targeted (other)|
|Strain of Origin||129S7/SvEvBrd-Hprt|
|Gene Symbol and Name||Del(5Limk1-Trim50)2Uta, deletion, Chr 5, Uta Francke 2|
|Molecular Note||Cre-mediated recombination of mice carrying Gtf2itm1Uta and Limk1tm2Uta removed all genomic sequence between the two alleles (including Gtf2i, Gtf2ird1, Clip2, Syna, Rfc2 Lat2, Eif4h and Limk1). [MGI Ref ID J:182796]|
Li HH; Roy M; Kuscuoglu U; Spencer CM; Halm B; Harrison KC; Bayle JH; Splendore A; Ding F; Meltzer LA; Wright E; Paylor R; Deisseroth K; Francke U. 2009. Induced chromosome deletions cause hypersociability and other features of Williams-Beuren syndrome in mice. EMBO Mol Med 1(1):50-65. [PubMed: 20049703] [MGI Ref ID J:182796]
Campuzano V; Segura-Puimedon M; Terrado V; Sanchez-Rodriguez C; Coustets M; Menacho-Marquez M; Nevado J; Bustelo XR; Francke U; Perez-Jurado LA. 2012. Reduction of NADPH-oxidase activity ameliorates the cardiovascular phenotype in a mouse model of Williams-Beuren Syndrome. PLoS Genet 8(2):e1002458. [PubMed: 22319452] [MGI Ref ID J:181479]
Goergen CJ; Li HH; Francke U; Taylor CA. 2011. Induced chromosome deletion in a Williams-Beuren syndrome mouse model causes cardiovascular abnormalities. J Vasc Res 48(2):119-29. [PubMed: 20926892] [MGI Ref ID J:182794]
Breeding & Husbandry Heterozygotes are viable and fertile, but homozyotes are not.
This strain is currently Awaiting Transfer from the Donor.View All Strains Awaiting Transfer from the Donor, In Progress and On Hold
|Wild-type from the colony|
|Considerations for Choosing Controls|
|Control Pricing Information for Genetically Engineered Mutant Strains.|
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