STOCK Gdf6^tm1Kng Tg(GDF6-cre/ERT2)L2Kng/J

Stock number: 031330
Product name: 6ax:pVBI347-L2
Research areas: Internal/Organ Research, Research Tools

Description

These 6ax:pVBI347-L2 compound mutant mice carry a targeted knock-out allele of the endogenous mouse Gdf6 gene in addition to a 3' GDF6 enhancer transgene derived from chimpanzee (lacking in humans) driving expression of tamoxifen-inducible cre recombinase (cre/ERT2).

Detailed description

Changes in bone morphogenetic protein (BMP) regulation are believed to cause the evolution of some skeletal traits. Evidence suggests that loss of a 3' non-coding GDH6 (growth differentiation factor 6) enhancer found in chimpanzees is related to digit shortening in human feet.

These 6ax:pVBI347-L2 compound mutant mice carry a targeted knock-out allele of the mouse Gdf6 gene (6ax) in addition to a transgene (pVBI347-L2) expressing the chimpanzee 3' GDF6 enhancer lacking in humans (human-conserved sequence deletion, hCONDEL.306). The enhancer drives expression of tamoxifen-inducible cre recombinase (cre/ERT2).

Crosses with Gt(ROSA)26Sor-lacZ reporter mice indicate that this GDF6 enhancer is expressed specifically in the muscle regulating the movement of the first digit of the foot (abductor hallicus). During development, the enhancer drives expression in the posterior of the embryo and in the posterior digits of the foot.

Mice homozygous for the Gdf6 knock-out allele are rarely viable and never fertile. Mice heterozygous for the mouse Gdf6 knock-out and hemizygous for the chimpanzee enhancer transgene show no overt phenotype. Animals homozygous or hemizygous for the transgene (and heterozygous for the Gdf6 knock-out) are viable and fertile.

Development

A vector carrying chimpanzee GDF6 3' enhancer hCONDEL.306 (human-conserved sequence deletion; chimpanzee chr8:94,899,638-94,894,864, panTro2 genome assembly) and an Hsp68-cre/ERT2 minimal promoter construct were injected into FVB embryos. The transgene copy number and insertion site are unknown. Resultant founder pVBI3147L2 mice were intercrossed with C57BL/6 background animals carrying a targeted knock-out of the mouse Gdf6 gene (6ax) in which exon 2 was replaced with a neomycin resistance cassette (see Stock No. 024648 for mixed B6;129 background mice).

Allele

Symbol: Gdf6^tm1Kng
Name: targeted mutation 1, David M Kingsley
MGI accession ID: MGI:2661063
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Gdf6^-
Marker symbol: Gdf6
Marker name: growth differentiation factor 6
Marker synonyms: BMP13; BMP-13; CDMP2; gdf16; KFM; KFS; KFS1; KFSL; SGM1; SYNS4
Chromosome: 4
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Site of expression: Inactivation of the Gdf6 gene causes defects in joint, ligament, and cartilage formation.
Molecular note: A genomic fragment containing exon 2 was replaced with a neomycin selection cassette inserted by homologous recombination. The deleted region encoded the entire mature signalling region and 120 amino acids of the pro region.

Allele

Symbol: Tg(GDF6-cre/ERT2)L2Kng
Name: transgene insertion L2, David M Kingsley
MGI accession ID: MGI:6093690
Generation method: Transgenic
Attributes: Recombinase-expressing; Inducible
Synonyms: hCONDEL.306-hsp-CreER-T2
Marker symbol: Tg(GDF6-cre/ERT2)L2Kng
Marker name: transgene insertion L2, David M Kingsley
Chromosome: UN
Strain of origin: FVB
Expressed genes: cre/ERT2,Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of expression: The GDF6 enhancer is expressed specifically in the muscle regulating the movement of the first digit of the foot (abductor hallicus).
Molecular note: A vector carrying chimpanzee GDF6 3' enhancer hCONDEL.306 (human-conserved sequence deletion; chimpanzee chr8:94,899,638-94,894,864, panTro2 genome assembly) and an Hsp68-cre/ERT2 minimal promoter construct were injected into FVB embryos. The transgene copy number and insertion site are unknown. Two independent stable lines (pVBI347L2 and pVBI347L3) were obtained. Resultant founder pVBI3147L2 mice were used for analysis.