Sh3gl1 (SH3-domain GRB2-like 1; also called endophilin A2 or endophilin 2) encodes a protein involved in clathrin-dependent endocytosis of synaptic vesicle membranes.
This knockout allele may be useful for studies of synapse physiology and synaptic vesicle cycling. Western blot analysis of brain, liver, heart, muscle, spleen and testis homogenates using isoform-specific antibody confirm a lack of expression. Homozygotes have a normal life span, are fertile, and show no obvious phenotypic defects, probably due to a functional compensation by endophilin 2 (Sh3gl1) and/or endophilin 3 (Sh3gl3).
When intercrossed with endophilin 1 targeted mutation animals (see Stock No. 021573) to create double knockout animals, pups appear normal at birth, but approximately 30% die within 24 hours. The remaining mice survived up to three weeks but have a compromised growth curve and major neurological defects, as revealed by poor motor coordination and spontaneous epileptic seizures.
Triple knockout pups developed from crosses of the endophilin 1 (see Stock No. 021573), endophilin 2 (this Stock No. 21574) and endophilin 3 (beta-actin Cre-crossed Stock No. 021575) 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.
