129S-Porcn^tm1.1Vdv/J

Stock number: 020994
Product name: Porcn-ex3-7Neo-flox)
Research areas: Developmental Biology Research, Endocrine Deficiency Research, Internal/Organ Research, Research Tools

Description

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).

Detailed description

These Porcn-ex3-7flox mutant mice possess loxP sites flanking exons 3-7 of the X-linked porcupine homolog (Porcn) gene. X^{Porcn-ex3-7flox}/X^{Porcn-ex3-7flox} females and X^{Porcn-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.

Development

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 X^{Porcn-ex3-7neo-flox}/X^{Porcn-ex3-7neo-flox} females and X^{Porcn-ex3-7neo-flox}/Y males maintained on a 129S background. Offspring were bred with 129S4/SvJaeSor-Gt(ROSA)26Sor^tm1(FLP1)Dym/J transgenic mice (Stock No. 003946) to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene to create X^{Porcn-ex3-7flox}/X^{Porcn-ex3-7flox} females and X^{Porcn-ex3-7flox}/Y males. Upon arrival, mice were bred to 129S1/SvImJ inbred mice (Stock No. 002448) for at least one generation.

Allele

Symbol: Porcn^tm1.1Vdv
Name: targeted mutation 1.1, Ignatia B Van den Veyver
MGI accession ID: MGI:5435556
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Porcn
Marker name: porcupine O-acyltransferase
Chromosome: X
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.