This Sh3gl1 (SH3-domain GRB2-like 1; also called endophilin A2 or endophilin 2) knockout allele may be useful for studies of synapse physiology and synaptic vesicle cycling.
Pietro De Camilli, Yale University School of Medicine, HHMI
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.
All coding exons following exon 1 (exons 2-10) were replaced with a neomycin resistance cassette in 129/SvJ-derived embryonic stem cells. This strain was backcrossed to C57BL/6 for 3 generations and maintained on a mixed genetic background composed of 129 and C57BL/6 by the donating laboratory.
|Allele Name||targeted mutation 1, Pietro De Camilli|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Endo-A2 null|
|Gene Symbol and Name||Sh3gl1, SH3-domain GRB2-like 1|
|Strain of Origin||129|
|Molecular Note||All coding exons following exon 1 (exons 2-10) were replaced with a neomycin resistance cassette. Western blot analysis confirmed the absence of protein expression in the brain.|
Homozygotes and heterozygotes are viable and fertile.
When using the B6;129-Sh3gl1tm1Pdc/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #021574 in your Materials and Methods section.