Quantitative trait locus analysis for chronic pancreatitis and diabetes mellitus in the WBN/Kob rat.
A causative gene mutation is still undefined in approximately half of patients with hereditary pancreatitis, and no genetic factor has been identified in most patients with sporadic chronic pancreatitis. To identify a pancreatitis-associated gene, we performed a quantitative trait locus (QTL) analysis for the traits of chronic pancreatitis and diabetes mellitus in WBN/Kob rats. We identified two highly significant QTLs for chronic pancreatitis and/or hyperinsulinemia on chromosomes 7 and X. These QTLs were located on completely different chromosomal regions from those of causative genes that have been reported for human chronic pancreatitis: PRSS1, CFTR, and SPINK1. For these QTLs, prevalences of the WBN/Kob allele significantly increased in the rats with chronic pancreatitis. These findings indicate that chronic pancreatitis in WBN/Kob rats is controlled by multiple genes, and a genetic analysis in WBN/Kob rats might be useful for gene targeting for human chronic pancreatitis.
Tsuji
A
A
Institute for Experimental Animals, Hamamatsu University School of Medicine, Handa-cho 3600, Hamamatsu, 431-3192, Japan.
Nishikawa
T
T
Mori
M
M
Suda
K
K
Nishimori
I
I
Nishimura
M
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000235:genetics; D002874:Chromosome Mapping; D002908:Chronic Disease; D003433:Crosses, Genetic; D003920:Diabetes Mellitus / Q000235:genetics* / Q000473:pathology; D005260:Female; D016678:Genome; D005838:Genotype; D007328:Insulin / Q000097:blood; D008297:Male; D018895:Microsatellite Repeats; D010195:Pancreatitis / Q000235:genetics* / Q000473:pathology; D019655:Quantitative Trait, Heritable; D051381:Rats; D011914:Rats, Inbred BN
D001786:Blood Glucose; D007328:Insulin