Isolation of a cDNA clone encoding a KATP channel-like protein expressed in insulin-secreting cells, localization of the human gene to chromosome band 21q22.1, and linkage studies with NIDDM.
The metabolism of glucose in insulin-secreting cells leads to closure of ATP-sensitive K+ channels (KATP), an event that initiates the insulin secretory process. Defects in insulin secretion are a common feature of non-insulin-dependent diabetes mellitus (NIDDM), and the beta-cell KATP that couples metabolism and membrane potential is a candidate for contributing to the development of this clinically and genetically heterogeneous disorder. We screened a hamster insulinoma cDNA library by low-stringency hybridization with a probe coding for the G-protein-coupled inwardly rectifying K+ channel GIRK1/KGA and isolated clones encoding a protein, KATP-2, whose sequence is 90% similar to that of the recently described KATP-1, an ATP-sensitive K+ channel expressed in heart and other tissues. RNA blotting showed that KATP mRNA was present in insulin-secreting cells and brain but not in heart. To assess the contribution of KATP-2 to the development of NIDDM, the human KATP-2 gene (symbol KCNJ7) was isolated and mapped to chromosome band 21q22.1 by fluorescence in situ hybridization. A simple tandem repeat DNA polymorphism, D21S1255, was identified in the region of the KATP-2 gene, and linkage studies between this marker and NIDDM were carried out in a group of Mexican-American sib pairs with NIDDM. There was no evidence for linkage between D21S1255 and NIDDM, indicating that KATP-2 is not a major susceptibility gene in this population.
Tsaur
M L
ML
Howard Hughes Medical Institute, University of California, San Francisco, USA.
Menzel
S
S
Lai
F P
FP
Espinosa
R
R
Concannon
P
P
Spielman
R S
RS
Hanis
C L
CL
Cox
N J
NJ
Le Beau
M M
MM
German
M S
MS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002891:Chromosomes, Human, Pair 21; D006224:Cricetinae; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D008040:Genetic Linkage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D018076:DNA, Complementary; D007328:Insulin; D015221:Potassium Channels; D012333:RNA, Messenger; D000255:Adenosine Triphosphate