Glu-47, which forms a salt bridge between neurophysin-II and arginine vasopressin, is deleted in patients with familial central diabetes insipidus

Journal Article · Wed Sep 01 04:00:00 EDT 1993 · Journal of Clinical Endocrinology and Metabolism; (United States)

DOI:https://doi.org/10.1210/jcem.77.3.8103767· OSTI ID:5044207

Yuasa, Hiromitsu; Ito, Masafumi; Nagasaki, Hiroshi; Oiso, Yutaka; Saito, Hidehiko ^[1]; Miyamoto, S; Sasaki, N ^[2]

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1. Nagoya Univ. School of Medicine, Chiba (Japan)
2. Chiba Children's Hospital, Chiba (Japan)

The arginine vasopressin (AVP) gene was sequenced in a pedigree with familial central diabetes insipidus (DI). When polymerase chain reaction-amplified DNAs from affected subjects were subjected to polyacrylamide gel electrophoresis, fragments including exon 2 displayed two additional, slower migrating bands. These extra bands represented DNA heteroduplexes, indicating that there was a deletion or insertion mutation in exon 2. As the region with such a mutation was identified by direct sequence analysis, polymerase chain reaction-amplified fragments including the region were subcloned and sequenced. A 3-basepair deletion (AGG) out of two consecutive AGG sequences (nucleotides 1824-1829) was identified in one of two alleles. The cosegregation of the mutation with the DI phenotype in the family was confirmed by restriction enzyme analyses. This mutation should yield an abnormal AVP precursor lacking Glu[sup 47] in its neurophysin-II (NP) moiety. Since Glu[sup 47] is essential for NP molecules to form a salt bridge with AVP, it is very likely that the function of NP as a carrier protein for AVP would be impaired. The authors suggest that AVP would undergo accelerated proteolytic degradation, and this mechanism would be involved in the pathogenesis of DI in this pedigree. 34 refs., 4 figs., 2 tabs.

• OSTI ID: 5044207
• Journal Information: Journal of Clinical Endocrinology and Metabolism; (United States), Journal Name: Journal of Clinical Endocrinology and Metabolism; (United States) Vol. 77:3; ISSN JCEMAZ; ISSN 0021-972X
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
BIOSYNTHESIS
CLONING
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
GENE MUTATIONS
HORMONES
HYBRIDIZATION
MOLECULAR STRUCTURE
MUTATIONS
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PITUITARY HORMONES
PROTEINS
RFLPS
STRUCTURAL CHEMICAL ANALYSIS
STRUCTURE-ACTIVITY RELATIONSHIPS
SYNTHESIS
VASOPRESSIN