The mitochondrial endophilin B1 protein, also known as endophilin B1 and SH3GLB1, encoded by the Sh3glb1 gene, interacts with BAX (BCL2-associated X protein) to regulate apoptosis and with BECN1 (beclin 1, autophagy related) to regulate autophagy and tumorigenesis. These bif-1 knock-out mice carry a mutant allele in which exon 1 and the translation initiation site have been replaced by a NEO cassette. Mutant null mice (6-18 months of age) on a mixed genetic background of 129SV/J and C57BL/6 exhibit enlarged spleens compared to wildtype controls. By 12 months of age, most homozygotes (almost 90%) develop spontaneous tumors. Lymphoma, hepatocellular carcinoma, sarcoma, esophageal squamous cell carcinoma, small cell lung carcinoma, and duodenal adenocarcinoma have been identified. . Moreover, homozygous mice on a C57BL/6 background develop obesity under both regular chow and high-fat diets and display a moderate impairment of insulin signaling. Fragmented depolarized mitochondria are observed in neurons from homozygotes. As a result of ischemic stroke (induced by middle cerebral artery occlusion), homozygotes exhibit larger infarcts and enhanced astrogliosis compared to wildtype controls. Cultured primary postnatal cortical neurons from homozygotes exhibit increased sensitivity to neurotoxic treatment, fewer mitochondria in neurites, and smaller, shorter mitochondria. In a model of autophagy-dependent clearance of damaged mitochondria, homozygotes respond with an accumulation of immature autophagosomes. Mice that are homozygous for the KO allele are viable and fertile. No gene product (protein) is detected by immunoblot analysis of homozygotes.
When crossed to a mouse model of B-cell lymphoma (see Stock No. 002728, for example), the double mutant mice (carrying the transgene and homozygous for the Sh3glb1tm1Hgw allele) exhibit accelerated tumor onset and mortality, chromosomal instability, and increased mitochondrial mass.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
