B6;129-Pcsk2^tm1Dfs/J

Stock number: 002963
Product name: SPC2-
Research areas: Diabetes and Obesity Research, Endocrine Deficiency Research, Metabolism Research

Description

These Pcsk2 knock-out mice exhibit impaired processing of three prohormones of the islets of Langerhans: proinsulin, proglucagon, and prosomatostatin. They are suitable for use in applications related to the study of the physiological roles of neuropeptides and peptide hormones.

Development

This strain was developed in the laboratory of Dr. Donald Steiner, HHMI Research Laboratories, The University of Chicago. Exon 3 of the Pcsk2 gene was interrupted using a vector containing the neo resistance gene. This results in a truncated transcript that is unstable, isn't secreted, and is unable to process protein precursors. The 129X1/SvJ x 129S1/Sv-derived R1 ES cell line was used for the targeted mutagenesis

Allele

Symbol: Pcsk2^tm1Dfs
Name: targeted mutation 1, Donald Steiner
MGI accession ID: MGI:1857445
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: PC2-; PC2KO; SPC2-
Marker symbol: Pcsk2
Marker name: proprotein convertase subtilisin/kexin type 2
Marker synonyms: 6330411F23Rik; NEC 2; Nec2; Nec-2; PC2; Phpp-2; prohormone convertase 2; SPC2
Chromosome: 2
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A neomycin resistance cassette was inserted into exon 3, which encodes the activation site at the junction of the propeptide and mature enzyme. RT-PCR experiments demonstrated that exon 3 was absent from transcripts produced from this allele, but Western blot analysis revealed the presence of a truncated protein of a size predicted by this mutation. However, no mature processed protein was detected and there was no evidence of enzyme activity in homozygous mice.
General note: Phenotypic Similarity to Human Syndrome: Pancreatic Neuroendocrine Tumors J:236511.