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GP2/THP gene family of self-binding, GPI-anchored proteins forms a cluster at chromosome 7F1 region in mouse genome.

Abstract：

:We investigated the genomic organization of pancreatic zymogen granule membrane-associated protein GP2, a GPI-anchored protein exhibiting self-aggregation at acidic pH, in order to construct a gene-knockout mouse. Cloning and analysis of lambda clones encoding GP2 from 129 Svj mouse genomic DNA libraries showed that the GP2 gene spans about 16.8 kb and includes 11 exons. Identifiable functional domains including a signal sequence, an EGF-like motif, a putative condensing ZP domain, a GPI-anchor attachment site, and a transmembrane sequence for GPI anchoring are encoded in separate exons. Using FISH, the GP2 gene was mapped to mouse chromosome 7F1 near the gene for THP, a GP2 homolog expressed in the cells of thick ascending loop of Henle (TALH) in the kidney. Further analysis of the mouse genome revealed that the THP and GP2 genes are adjacent to one another and are separated by only 3.5 kb in the 7F1 locus. Additionally, the overall structure of the THP gene, 16.2kb with 11 exons, was strikingly similar to that of GP2. This finding suggests that the GP2 and THP genes were generated by gene duplication and evolved separately to acquire regulatory elements leading to tissue-specific expression. Comparative analysis revealed that the 5' flanking region of the THP gene is similar to the first intron of NKCC2, a TALH cell-specific ion-transporter gene. The promoter region of the GP2 gene shares cis-elements found in other pancreas-specific genes. Using this genetic information, a GP2 null mutation was successfully introduced into an ES cell line, and an animal model was established without disruption of THP expression.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kobayashi K,Yanagihara K,Ishiguro K,Fukuoka S

doi

10.1016/j.bbrc.2004.07.197

subject

Has Abstract

pub_date

2004-09-17 00:00:00

pages

659-64

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(04)01591-8

journal_volume

322

pub_type

杂志文章

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