| First Author | Muhsin NIA | Year | 2020 |
| Journal | Mamm Genome | Volume | 31 |
| Issue | 1-2 | Pages | 17-29 |
| PubMed ID | 31974728 | Mgi Jnum | J:285767 |
| Mgi Id | MGI:6394171 | Doi | 10.1007/s00335-020-09826-4 |
| Citation | Muhsin NIA, et al. (2020) A novel mutation in the mouse Pcsk1 gene showing obesity and diabetes. Mamm Genome 31(1-2):17-29 |
| abstractText | The proprotein convertase subtilisin/Kexin type 1 (PCSK1/PC1) protein processes inactive pro-hormone precursors into biologically active hormones in a number of neuroendocrine and endocrine cell types. Patients with recessive mutations in PCSK1 exhibit a complex spectrum of traits including obesity, diarrhoea and endocrine disorders. We describe here a new mouse model with a point mutation in the Pcsk1 gene that exhibits obesity, hyperphagia, transient diarrhoea and hyperproinsulinaemia, phenotypes consistent with human patient traits. The mutation results in a pV96L amino acid substitution and changes the first nucleotide of mouse exon 3 leading to skipping of that exon and in homozygotes very little full-length transcript. Overexpression of the exon 3 deleted protein or the 96L protein results in ER retention in Neuro2a cells. This is the second Pcsk1 mouse model to display obesity phenotypes, contrasting knockout mouse alleles. This model will be useful in investigating the basis of endocrine disease resulting from prohormone processing defects. |
