Genetic analysis of pancreatic duct hyperplasia in Otsuka Long-Evans Tokushima Fatty rats: Possible association with a region on rat chromosome 14 that includes the disrupted cholecystokinin-A receptor gene

Naohide Kanemoto, Mari Kondo, Tomoyuki Iwanaga, Haretsugu Hishigaki, Toshihide Ono, Ayako Mizoguchi-Miyakita, Keiko Oga, Atsushi Tsuji, Shiro Okuno, Takeshi K. Watanabe, Masato Nose, Akira Tanigami

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

An Otsuka Long-Evans Tokushima Fatty (OLETF) strain of rat spontaneously developed hyperglycemia, hyperinsulinemia, insulin resistance and mild obesity, which had been studied as animal model for type II diabetes mellitus (T2DM). Recently, we observed that this strain coincidentally developed atypical hyperplasia of the choledocho-pancreatic ductal epithelium with a complete incidence. In an effort to locate genes responsible for this hyperplasia, we prepared 288 backcross progeny from a mating between OLETF rats and BN rats (which do not develop hyperplasia), and performed a genome-wide scan using 207 polymorphic genetic markers. We observed a prominent association of hyperplasia with a region involving a marker locus D14Mit4 (P = 0.00020, Fisher's exact test) and Cckar(the cholecystokinin-A receptor gene; P= 0.00025, Fisher's exact test) which is known to be disrupted in an OLETF strain. Our findings indicated that epithelial hyperplasia of the choledochopancreatic duct is associated with a region on rat chromosome 14 around the Cckar gene in an additive fashion with another two susceptible loci, each on chromosome 9 and 7. This implied the possibility that Cckar deficiency could result in a predisposition towards pancreatic duct hyperplasia.

Original languageEnglish
Pages (from-to)133-139
Number of pages7
JournalPathology international
Volume51
Issue number3
DOIs
Publication statusPublished - 2001

Keywords

  • Cckar
  • Otsuka Long-Evans Tokushima Fatty rat
  • Pancreatic duct hyperplasia
  • Rat chromosome 14

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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