ABSTRACT
In 404 Lep(ob/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 Lep(ob). The phenotypes of B6.DBA congenic mice include reduced beta-cell replication rates accompanied by reduced beta-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.
Subject(s)
Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease , Receptors, Cell Surface/genetics , Amino Acid Sequence , Animals , Base Sequence , Blood Glucose/genetics , Chromosomes, Mammalian , Cloning, Molecular , Crosses, Genetic , Glucose Tolerance Test/methods , Haplotypes , Homozygote , Insulin/blood , Male , Mice , Mice, Congenic , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, Obese , Molecular Sequence Data , Mutation , Protein Isoforms/chemistry , Protein Isoforms/genetics , Quantitative Trait LociABSTRACT
Tc insolubilization in four soils samples was compared by pre-incubating them in both dry and wet states, then measuring Tc concentrations in solution when the samples were saturated with an excess of water spiked with 99Tc. Soils pre-incubated in a dry state showed higher Tc insolubilization than soils incubated in a wet state. To clarify the difference in Tc insolubilization, Eh, bacterial abundances, and bacterial species compositions in the dry and wet ponding water samples were determined. For the wet ponding water samples, Eh values were forced to decrease, but no increase in Tc insolubilization was observed. The dry and wet ponding water samples had similar numbers of bacteria. However, denaturing gradient gel electrophoresis analysis revealed that they had different bacterial species compositions. These results suggested the difference in bacterial species compositions would account for the difference in Tc insolubilization.
