STOCK Megf8^tm1.2Ddg/J

Stock number: 025417
Research areas: Neurobiology Research, Research Tools

Description

This strain carries a floxed allele of Megf8, identified as a novel modifier of BMP4 (bone morphogenetic protein 4) signaling in trigeminal ganglion (TG) neurons. Cre excision of the floxed region creates a knockout of the gene.

Detailed description

Megf8 (multiple EGF-like-domains 8) is widely expressed during early embryonic development with strong expression in the somites, limb buds, primordial gut, developing eye, and pharyngeal arches. Throughout embryogenesis and into the postnatal period, MEGF8 is present in the sensory neurons of the dorsal root ganglion and trigeminal ganglion, as well as the central nervous system including the developing neuroepithelium, postnatal hippocampus, layer 4/5 of the cortex and the olfactory bulb. Megf8 has been identified as a novel modifier of BMP4 (bone morphogenetic protein 4) signaling in trigeminal ganglion (TG) neurons. TG axon growth is robustly inhibited by BMP4, and this inhibition is dependent on MEGF8 expression.

The last exon of Megf8 is flanked by loxP sites in this conditional mutant strain. Cre excision of the floxed region creates a knockout of the gene. Loss of MEGF8 disrupts axon guidance in the peripheral nervous system and leads to defects in development of the limb, heart, and left-right patterning, defects that resemble those observed in BMP4 loss-of-function mice.

Development

The final exon, comprising the transmembrane domain, intracellular C-terminus, and 3' UTR, was flanked with loxP sites. The 5' loxP site was introduced 500 bp upstream of the exon. The 3' loxP site, incorporated in an frt-neomycin-frt-loxP cassette was place 500 bp downstream of the exon. The targeted mutation was created in 129S6/SvEvTac-derived embryonic stem (ES) cells. Resultant male carriers were then mated with the FlpE females to excise the neomycin cassette and generate the conditional allele. This strain was maintained on a mixed genetic background involving CD1 by the donating lab.

Allele

Symbol: Megf8^tm1.2Ddg
Name: targeted mutation 1.2, David D Ginty
MGI accession ID: MGI:5558931
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Megf8
Marker name: multiple EGF-like-domains 8
Chromosome: 7
Strain of origin: 129S6/SvEvTac
Molecular note: The final exon was flanked by a loxP site and an FRT-flanked neomycin resistance cassette with a 3' loxP site. Flp-mediated recombination removed the selection cassette and left the last exon floxed.