Please use this identifier to cite or link to this item: 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
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
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