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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
Author(s) -
Kanemoto Naohide,
Kondo Mari,
Iwanaga Tomoyuki,
Hishigaki Haretsugu,
Ono Toshihide,
MizoguchiMiyakita Ayako,
Oga Keiko,
Tsuji Atsushi,
Okuno Shiro,
Watanabe Takeshi K.,
Nose Masato,
Tanigami Akira
Publication year - 2001
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1046/j.1440-1827.2001.01176.x
Subject(s) - hyperplasia , endocrinology , medicine , cholecystokinin receptor , cholecystokinin , pancreatic duct , biology , pancreas , receptor
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 choledocho‐pancreatic 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.