These mice carry a floxed allele of the Sh3gl3 (SH3-domain GRB2-like 3; also called endophilin A3 or endophilin 3) gene. Cre excision of loxP-flanked exon 1 enables the generation of tissue-specific knockouts. This strain may be useful for studies of synapse physiology and synaptic vesicle cycling.
Pietro De Camilli, Yale University School of Medicine, HHMI
Sh3gl3 (SH3-domain GRB2-like 3; also called endophilin A3 or endophilin 3) encodes a protein involved in clathrin-dependent endocytosis of synaptic vesicle membranes.
Exon 1 of the gene is flanked by loxP sites in this conditional mutant allele. Cre excision of the floxed segment can generate tissue-specific knockouts of the gene and may be useful for studies of synapse physiology and synaptic vesicle cycling.
Homozygous knockouts of the gene (created through crosses with a beta-actin Cre mouse) have a normal life span, are fertile, and show no obvious phenotypic defects, probably due to a functional compensation by endophilin 1 (Sh3gl2) and/or endophilin 2 (Sh3gl1).
Triple knockout pups developed from crosses of the endophilin 1 (see Stock No. 021573), endophilin 2 (see Stock No. 021574), and endophilin 3 (beta-actin Cre-crossed Stock No. 21575) mutations are born at predicted Mendelian ratios, but are slightly smaller at birth, have breathing problems and die immediately or within a few hours of birth. Synaptic transmission is impaired, but not abolished. Triple mutant mice that are heterozygous for a knockout of endophilin 2 survive to adulthood, but have severe epileptic seizures.
A conditional targeting vector was made by flanking a 1.8kb region containing exon 1 with loxP sites and inserting an FRT site-flanked neomycin-loxP cassette in reverse transcriptional orientation into intron 1. The targeting vector was electroporated into hybrid C57BL/6J-129S1/Sv mouse embryonic stem cells. Chimeric animals were mated to a FLPe recombinase deleter strain to remove the neomycin selection cassette. This strain was maintained on a mixed 129 and C57BL/6J genetic background by the donating lab.
|Allele Name||targeted mutation 1.1, inGenious Targeting Laboratory|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Sh3gl3, SH3-domain GRB2-like 3|
|Strain of Origin||C57BL/6J x 129S1/Sv|
|Molecular Note||A conditional targeting vector was made by flanking a 1.8kb region containing exon 1 with loxP sites and inserting an FRT site-flanked neomycin-loxP cassette in reverse transcriptional orientation into intron 1. Flp-mediated recombination removed the neo cassette.|
Homozygotes and heterozygotes are viable and fertile.
When using the B6;129-Sh3gl3tm1.1Itl/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #021575 in your Materials and Methods section.