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https://doi.org/10.1371/journal.pgen.1000137
Title: | Positional cloning of "Lisch-like", a candidate modifier of susceptibility to type 2 diabetes in mice | Authors: | Dokmanovic-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. |
Keywords: | glucose hemoglobin A1c immunoglobulin protein 14 3 3 cell surface receptor insulin isoprotein lisch like protein, mouse lisch-like protein, mouse animal cell animal experiment animal model animal tissue article C57BL 6 mouse cell division chromosome 1q congenic strain controlled study DBA 2 mouse embryo gene expression genetic susceptibility molecular cloning mouse non insulin dependent diabetes mellitus nonhuman nucleotide sequence null allele orthology pancreas islet pancreas islet beta cell protein domain quantitative trait locus sequence analysis zebra fish amino acid sequence animal blood C57BL mouse chemistry chromosome cross breeding DBA mouse experimental diabetes mellitus genetic predisposition genetics glucose blood level glucose tolerance test haplotype homozygote male methodology molecular genetics mouse mutant mutation non insulin dependent diabetes mellitus Danio rerio Mus Amino Acid Sequence Animals Base Sequence Blood Glucose Chromosomes, Mammalian Cloning, Molecular Crosses, Genetic Diabetes Mellitus, Experimental Diabetes Mellitus, Type 2 Genetic Predisposition to Disease Glucose Tolerance Test Haplotypes Homozygote Insulin Male Mice Mice, Congenic Mice, Inbred C57BL Mice, Inbred DBA Mice, Obese Molecular Sequence Data Mutation Protein Isoforms Quantitative Trait Loci Receptors, Cell Surface |
Issue Date: | 2008 | Citation: | Dokmanovic-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 | Rights: | Attribution 4.0 International | Abstract: | In 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. | Source Title: | PLoS Genetics | URI: | https://scholarbank.nus.edu.sg/handle/10635/161686 | ISSN: | 15537390 | DOI: | 10.1371/journal.pgen.1000137 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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