This strain contains floxed exons in the X-linked Porcn gene and may be useful for studying developmental defects associated with Focal dermal hypoplasia (Goltz syndrome).
Ignatia B. Van den Veyver, Baylor College of Medicine
These Porcn-ex3-7flox mutant mice possess loxP sites flanking exons 3-7 of the X-linked porcupine homolog (Porcn) gene. XPorcn-ex3-7flox/XPorcn-ex3-7flox females and XPorcn-ex3-7flox/Y males are viable and fertile. PORCN encodes an endoplasmic reticulum protein involved in wingless-related MMTV (Wnt) signaling and has an essential role in gastrulation during early embryonic development. Dominant loss-of-function mutations in PORNC have been associated with focal dermal hypoplasia (FDH), also known as Goltz syndrome or Goltz-Gorlin syndrome, an X-linked disorder that predominantly affects females. FDH is characterized by a wide array of abnormalities including defects of skeleton, skin, hair, eyes, ears, and ectodermal appendages. When bred to mice that express Cre recombinase, resulting offspring will have exons 3-7 deleted in the cre-expressing tissues. Widespread deletion results in increased early embryonic lethality.
When bred to B6.Cg-Tg(Prrx1-cre)1Cjt/J mice (Stock No. 005584), mesenchyme-specific cre-expression results in mice exhibiting FDH-like limb shortening. Defects were more severe in forelimbs.
When bred to Tg(EIIa-cre)C5379Lmgd mice (Stock No. 003724), expression in the early mouse embryo results in partial lethality and decreased hairgrowth.
A targeting vector was designed to insert a loxP site upstream of exon 3, and a second loxP site followed by a frt-flanked neomycin resistance (neo) cassette downstream of exon 7, of the X-linked porcupine homolog (Porcn) gene. The construct was electroporated into 129S5/SvEvBrd-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric males were bred to 129S females. The resulting in a colony contained XPorcn-ex3-7neo-flox/XPorcn-ex3-7neo-flox females and XPorcn-ex3-7neo-flox/Y males maintained on a 129S background. Offspring were bred with 129S4/SvJaeSor-Gt(ROSA)26Sortm1(FLP1)Dym/J transgenic mice (Stock No. 003946) to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene to create XPorcn-ex3-7flox/XPorcn-ex3-7flox females and XPorcn-ex3-7flox/Y males. Upon arrival, mice were bred to 129S1/SvImJ inbred mice (Stock No. 002448) for at least one generation.
|Allele Name||targeted mutation 1.1, Ignatia B Van den Veyver|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Porcn, porcupine O-acyltransferase|
|Strain of Origin||129S5/SvEvBrd|
|Molecular Note||A loxP site was inserted upstream of exon 3 and a loxP site and FRT flanked neo cassette were inserted downstream of exon 7. Flp mediated recombination removed the neo cassette.|
When maintaining a live colony, homozygous females may be bred to hemizygous males. This gene is x-linked.
When using the Porcn-ex3-7Neo-flox) mouse strain in a publication, please cite the originating article(s) and include JAX stock #020994 in your Materials and Methods section.