C57BL/6J-Phb2^em1Blev/J

Stock number: 035847
Product name: Phb2mLIR KI
Research areas: Cell Biology Research, Developmental Biology Research

Description

Phb2mLIR KI mice carry Y121A and L124A mutations in the LC3-interacting region of the mouse Phb2 (prohibitin 2) gene. They are useful in a range of studies, including mitophagy and early embryonic development.

Detailed description

Prohibitin 2 (PHB2) is an inner mitochondrial membrane protein that is a crucial mitophagy receptor involved in targeting mitochondria for autophagic degradation. PHB2 binds the autophagosomal membrane-associated protein LC3 through an LC3-interaction region (LIR) domain upon mitochondrial depolarization and proteasome-dependent outer membrane rupture. PHB2 is required for Parkin-induced mitophagy in mammalian cells and for the clearance of paternal mitochondria after embryonic fertilization in C. elegans.

These Phb2mLIR KI mice carry Y121A (TAC to GCG) and L124A (CTA to GCC) mutations in the LC3-interacting region of the mouse Phb2 (prohibitin 2) gene. Heterozygotes are viable and fertile. Homozygotes are embryonic lethal, failing to develop past E7.5-E8.5. Protein levels appear normal in mouse embryonic fibroblasts (MEFs). No further characterization of these mice has been carried out as of December 2020.

Mouse cell line studies involving these same mutations (Wei Y, et al. Cell. 2017 Jan 12;168(1-2):224-238. PMID: 28017329) have confirmed that the PHB2 LIR domain Y121A/L124A mutations block GST-tagged PHB2 pull-down of LC3-II in okadaic acid (OA)-treated HeLa/Parkin cell lysates with knockdown of endogenous PHB1 (prohibitin 1) and PHB2. Evidence suggests the LIR domain of PHB2 regulates direct binding to LC3 in vitro and binding to LC3-II in HeLa cells during mitophagy-inducing conditions.

Development

Y121A (TAC to GCG) and L124A (CTA to GCC) mutations were introduced to the LC3-interacting region in exon 4 of the mouse Phb2 (prohibitin 2) gene though CRISPR/Cas9 methodologies. These mutations were created in C57BL/6J embryos. This line was further backcrossed to C57BL/6J for 5 generations by the donating laboratory.

Allele

Symbol: Phb2^em1Blev
Name: endonuclease-mediated mutation 1, Beth Levine
MGI accession ID: MGI:6479051
Generation method: Endonuclease-mediated
Attributes: Not Applicable
Synonyms: Phb2mLIR KI
Marker symbol: Phb2
Marker name: prohibitin 2
Marker synonyms: BAP; Bap37; Bap-37; Bcap27; Bcap37; hBAP; p22; PNAS-141; REA; repressor of estrogen receptor activity
Chromosome: 6
Strain of origin: C57BL/6J
Molecular note: CRISPR/cas9 genome editing is used to introduce the Y121A (TAC to GCG) and L124A (CTA to GCC) mutations into the LC3-interacting region in exon 4.