Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pgen.1000137
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dc.titlePositional cloning of "Lisch-like", a candidate modifier of susceptibility to type 2 diabetes in mice
dc.contributor.authorDokmanovic-Chouinard M.
dc.contributor.authorChung W.K.
dc.contributor.authorChevre J.-C.
dc.contributor.authorWatson E.
dc.contributor.authorYonan J.
dc.contributor.authorWiegand B.
dc.contributor.authorBromberg Y.
dc.contributor.authorWakae N.
dc.contributor.authorWright C.V.
dc.contributor.authorOverton J.
dc.contributor.authorGhosh S.
dc.contributor.authorSathe G.M.
dc.contributor.authorAmmala C.E.
dc.contributor.authorBrown K.K.
dc.contributor.authorIto R.
dc.contributor.authorLeDuc C.
dc.contributor.authorSolomon K.
dc.contributor.authorFischer S.G.
dc.contributor.authorLeibel R.L.
dc.date.accessioned2019-11-06T09:37:52Z
dc.date.available2019-11-06T09:37:52Z
dc.date.issued2008
dc.identifier.citationDokmanovic-Chouinard M., Chung W.K., Chevre J.-C., Watson E., Yonan J., Wiegand B., Bromberg Y., Wakae N., Wright C.V., Overton J., Ghosh S., Sathe G.M., Ammala C.E., Brown K.K., Ito R., LeDuc C., Solomon K., Fischer S.G., Leibel R.L. (2008). Positional cloning of "Lisch-like", a candidate modifier of susceptibility to type 2 diabetes in mice. PLoS Genetics 4 (7) : e1000137. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pgen.1000137
dc.identifier.issn15537390
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161686
dc.description.abstractIn 404 Lepob/ob F2 progeny of a C57BL/6J (B6) x DBA/2J (DBA) intercross, we mapped a DBA-related quantitative trait locus (QTL) to distal Chr1 at 169.6 Mb, centered about D1Mit110, for diabetes-related phenotypes that included blood glucose, HbA1c, and pancreatic islet histology. The interval was refined to 1.8 Mb in a series of B6.DBA congenic/subcongenic lines also segregating for Lepob. The phenotypes of B6.DBA congenic mice include reduced ?-cell replication rates accompanied by reduced ?-cell mass, reduced insulin/glucose ratio in blood, reduced glucose tolerance, and persistent mild hypoinsulinemic hyperglycemia. Nucleotide sequence and expression analysis of 14 genes in this interval identified a predicted gene that we have designated "Lisch-like" (Ll) as the most likely candidate. The gene spans 62.7 kb on Chr1qH2.3, encoding a 10-exon, 646-amino acid polypeptide, homologous to Lsr on Chr7qB1 and to Ildr1 on Chr16qB3. The largest isoform of Ll is predicted to be a transmembrane molecule with an immunoglobulin-like extracellular domain and a serine/threonine-rich intracellular domain that contains a 14-3-3 binding domain. Morpholino knockdown of the zebrafish paralog of Ll resulted in a generalized delay in endodermal development in the gut region and dispersion of insulin-positive cells. Mice segregating for an ENU-induced null allele of Ll have phenotypes comparable to the B.D congenic lines. The human ortholog, C1orf32, is in the middle of a 30-Mb region of Chr1q23-25 that has been repeatedly associated with type 2 diabetes. © 2008 Dokmanovik-Chouinard et al.
dc.sourceUnpaywall 20191101
dc.subjectglucose
dc.subjecthemoglobin A1c
dc.subjectimmunoglobulin
dc.subjectprotein 14 3 3
dc.subjectcell surface receptor
dc.subjectinsulin
dc.subjectisoprotein
dc.subjectlisch like protein, mouse
dc.subjectlisch-like protein, mouse
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectarticle
dc.subjectC57BL 6 mouse
dc.subjectcell division
dc.subjectchromosome 1q
dc.subjectcongenic strain
dc.subjectcontrolled study
dc.subjectDBA 2 mouse
dc.subjectembryo
dc.subjectgene expression
dc.subjectgenetic susceptibility
dc.subjectmolecular cloning
dc.subjectmouse
dc.subjectnon insulin dependent diabetes mellitus
dc.subjectnonhuman
dc.subjectnucleotide sequence
dc.subjectnull allele
dc.subjectorthology
dc.subjectpancreas islet
dc.subjectpancreas islet beta cell
dc.subjectprotein domain
dc.subjectquantitative trait locus
dc.subjectsequence analysis
dc.subjectzebra fish
dc.subjectamino acid sequence
dc.subjectanimal
dc.subjectblood
dc.subjectC57BL mouse
dc.subjectchemistry
dc.subjectchromosome
dc.subjectcross breeding
dc.subjectDBA mouse
dc.subjectexperimental diabetes mellitus
dc.subjectgenetic predisposition
dc.subjectgenetics
dc.subjectglucose blood level
dc.subjectglucose tolerance test
dc.subjecthaplotype
dc.subjecthomozygote
dc.subjectmale
dc.subjectmethodology
dc.subjectmolecular genetics
dc.subjectmouse mutant
dc.subjectmutation
dc.subjectnon insulin dependent diabetes mellitus
dc.subjectDanio rerio
dc.subjectMus
dc.subjectAmino Acid Sequence
dc.subjectAnimals
dc.subjectBase Sequence
dc.subjectBlood Glucose
dc.subjectChromosomes, Mammalian
dc.subjectCloning, Molecular
dc.subjectCrosses, Genetic
dc.subjectDiabetes Mellitus, Experimental
dc.subjectDiabetes Mellitus, Type 2
dc.subjectGenetic Predisposition to Disease
dc.subjectGlucose Tolerance Test
dc.subjectHaplotypes
dc.subjectHomozygote
dc.subjectInsulin
dc.subjectMale
dc.subjectMice
dc.subjectMice, Congenic
dc.subjectMice, Inbred C57BL
dc.subjectMice, Inbred DBA
dc.subjectMice, Obese
dc.subjectMolecular Sequence Data
dc.subjectMutation
dc.subjectProtein Isoforms
dc.subjectQuantitative Trait Loci
dc.subjectReceptors, Cell Surface
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1371/journal.pgen.1000137
dc.description.sourcetitlePLoS Genetics
dc.description.volume4
dc.description.issue7
dc.description.pagee1000137
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