These OVE1498 mice have a deletion of 66.8 kbp in mouse chromosome 18, including the entire coding region of the serine peptidase inhibitor, Kazal type 5 gene (Spink5). By embryonic day (E)17.5, homozygous embryos show fragile stratum corneum. Homozygotes exhibit perinatal death due to dehydration. These OVE1498 mice are a model system for molecular studies of desmosomal stability and keratinocyte adhesion, and for designing therapeutic strategies to treat the human autosomal recessive skin disease Netherton syndrome.
Paul A Overbeek, Baylor College of Medicine
Dr. Thomas Bugge, NIH/NIDCR
By embryonic day (E)17.5, homozygous embryos show fragile stratum corneum. Homozygous mice exhibit perinatal death due to dehydration (dehydrated corpses within 24 h after birth). This phenotype is a consequence of desmosomal fragility associated with premature proteolysis of corneodesmosin, an extracellular desmosomal component. This mouse mutant provides a model system for molecular studies of desmosomal stability and keratinocyte adhesion, and for designing therapeutic strategies to treat the human autosomal recessive skin disease Netherton syndrome (NS). The expected coat color is agouti.
The transposon vector pT-Tybs-3u2032E was designed with left IR/DR (280bp)::Tyro(4.1kb)::right IR/DR(280bp). The 4.1 kb tyrosinase minigene isolated from plasmid TyBS (Yokoyama et al., 1990) was inserted into pT Sleeping Beauty transposon (Ivics et al. 1997). The 2.7kb PGK2-SB10 transgene was designed with mouse phosphoglycerol kinase 2 promotor, coding sequences for the Sleeping Beauty transposase (SB10; see Ivics et al 1997), and Xenopus β-globin polyA signal. The pT-Tybs-3'E transgene and the PGK2-SB10 transgene were co-injected into FVB/N embryos. Chimeric mice were bred to FVB/N mice. Pigmented transgenic founder mice (line OVE1498) were bred together. These mice have a (transposition-induced??) deletion of 66.8 kb in mouse chromosome 18, including the entire coding region (exons 1-32) of the serine peptidase inhibitor, Kazal type 5 (Spink5) gene. Original integration site is chr.18 (agenic region 3.8 kb upstream from the start codon of Spink5). Transposed integration site is chr.18 (agenic region 6 kb downstream from the stop codon of Spink5). Mice are agouti. Prior to 2013, mice were sent from Dr. Overbeek to Dr. Thomas Bugge (NIH/NIDCR). In 2013, Dr. Bugge sent mice to The Jackson Laboratory Repository node of MMRRC.
|Allele Name||transposon insertion 1498, Paul A Overbeek|
|Allele Type||Transposon induced|
|Gene Symbol and Name||Spink5, serine peptidase inhibitor, Kazal type 5|
|Strain of Origin||FVB/N|
|Molecular Note||A transposon transgene containing mouse Pgk2 driving expression of sleeping beauty 10 (SB10) and a mouse tyrosinase minigene driven by a Tyr enhancer flanked by Sleeping Beauty inverted repeats (termedpT-Tybs-3'E) were co-injected with a Pgk2 driven SB10. In line 1498, transposon and transposase co-integration results in a 66.8 kb deletion containing the coding exons of the targeted gene and none of the coding regions of the genes flanking the integration site. RT-PCR confirmed the absence of transcript expression at P0 skin cDNA.|
|Mutations Made By|| |
Paul Overbeek, Baylor College of Medicine
Homozygous mice die in the first 24 hours after birth. When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to FVB/NJ inbred mice. The expected coat color is agouti.
When using the FVB/N-Spink5Tn(Pgk2-sb10,sb-Tyr)1498Ove/BugMmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36522 in your Materials and Methods section.
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