The Pask gene is disrupted by the insertion of an IRES-β-geo fusion cassette in these knockin/knockout mice. LacZ is detected in testis and homozygotes exhibit a range of metabolic traits.
Roland Wenger, University of Zurich
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Null/Knockout) | Pask | PAS domain containing serine/threonine kinase |
A splice acceptor site and an IRES-β-geo fusion cassette replace exons 10-14 of the PAS domain containing serine/threonine kinase (Pask) gene in these mutant mice. Gene function is abolished. PASK is a serine/threonine kinase which regulates energy homeostasis and acts as a cellular metabolic sensor. In wildtype mice, PASK is expressed in post-meiotic germ cells during spermatogenesis, with typically low level ubiquitous expression. Homozygous Pask-/- mice are viable, fertile, and normal in size, with lacZ staining visible in the testis beginning at 25 days of age. These mice exhibit impaired glucose-stimulated insulin secretion with no change in islet size or morphology. Increased O2 consumption, CO2 production, and heat generation is also observed. On a high-fat diet, Pask-/- mice have reduced liver triglyceride levels and show little difference in glucose tolerance, insulin resistance, or weight gain compared to wildtype mice.
A targeting vector was designed to replace exons 10-14 of the PAS domain containing serine/threonine kinase (Pask) gene with a splice acceptor site, an internal ribosome entry site (IRES), and a neomycin-β-galactosidase fusion protein (β-geo). The construct was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into (C57BL/6 x DBA)F1 blastocysts and the resulting chimeric males were bred to C57BL/6 females. These mice were backcrossed at least 10 generations to C57BL/6J background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
Expressed Gene | Bgeo, fusion of beta-galactosidase and neomycin phosphotransferase genes, E. coli |
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Site of Expression | lacZ staining visible in the testis beginning at 25 days of age. |
Allele Name | targeted mutation 1, Roland H Wenger |
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Allele Type | Targeted (Reporter, Null/Knockout) |
Allele Synonym(s) | PASK-; Paskin- |
Gene Symbol and Name | Pask, PAS domain containing serine/threonine kinase |
Gene Synonym(s) | |
Expressed Gene | Bgeo, fusion of beta-galactosidase and neomycin phosphotransferase genes, E. coli |
Site of Expression | lacZ staining visible in the testis beginning at 25 days of age. |
Strain of Origin | 129S6/SvEvTac |
Chromosome | 1 |
Molecular Note | Exons 10 through 14 were replace with a cassette containing a splice acceptor site and IRES-beta-geo. Norhtern blot analysis of various tissues confirmed the absence of endogenous transcript and identified mutant transcript containing the beta-geo squenence. |
Mutations Made By | Roland Wenger, University of Zurich |
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.129S6-Pasktm1Weng/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017709 in your Materials and Methods section.
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Heterozygous for Pask<tm1Weng> |
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