Scott syndrome is a rare mild bleeding disorder caused by an inability of cells to expose phosphatidylserine (which binds to plasma clotting factors) upon platelet or endothelial cell activation. The ANO6 (anoctamin 6; also called TMEM16F) gene has been implicated.
This genetrap of mouse Ano6, incorporating βgeo (beta-galactosidase/neomycin) and antiparallel recombination sites, is a knockout allele. Immunohistochemical staining with an anti-beta-galactosidase antibody does not provide a signal. Heterozygotes are viable and fertile, but, on this C57BL/6 genetic background, homozygotes die at birth.
Heterozygous breeding of C57BL/6 background mutant mice crossed to 129X1/SvJ for one generation (B6129X1F1 background mice) produces some viable homozygous progeny (8% homozygous pups versus the predicted Mendelian 25%). Subsequent crosses of these viable homozygous "rescues" are reported to demonstrate expected Mendelian inheritance.
German Gene Trap Consortium (GGTC) vector FlipROSAbetageo was introduced to C57BL/6NTac-derived JM8 embryonic stem (ES) cells to create the European Conditional Mouse Mutagenesis (EUCOMM) mutant ES cell line EUCJ0166e09. The vector incorporates a splice acceptor (SA)-βgeo-polyA cassette flanked by frt-f3-loxP-lox511 sites 5' of the SA and loxP-lox511-frt-f3 sites in reverse orientation 3' of the polyA. ES cells were introduced to embryos derived from B6(Cg)-Tyrc-2J/J mice (see Stock No. 000058). Resultant chimeric mice were backcrossed to C57BL/6N for three generations by the donating lab. This genetrap inactivates the Ano6 (TMEM16F) gene and the antiparallel recombination sites enable the flipping of the genetrap without its excision.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
|Allele Name||gene trap EUCJ0166e09, Helmholtz Zentrum Muenchen GmbH|
|Allele Type||Gene trapped|
|Gene Symbol and Name||Ano6, anoctamin 6|
|Strain of Origin||C57BL/6N|
|Molecular Note||Trapped gene association determined by genome coordinate overlap and strand.|
Heterozygotes are viable and fertile. Homozygotes on the C57BL/6 background die at birth.
When using the C57BL/6-Ano6Gt(EUCJ0166e09)Hmgu/DgiJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #024798 in your Materials and Methods section.