Functional polymorphisms in inbred rat strains and their allele frequencies in commercially available outbred stocks

Abstract

Polymorphisms that have been proven to influence gene functions are called functional polymorphisms. It is significant to know the distribution of functional polymorphisms in the rat, widely used in animal models for human diseases. In this study, we assessed 16 functional polymorphisms consisting of 3 coat color and 13 disease-associated genes in 136 rat strains, as a part of the genetic profiling program of the National Bio Resource Project for the Rat (NBRP-Rat). Polymorphisms of Cdkn1a, Fcgr3, Grp10, Lss, and Fdft1, which were proven to function in prostate tumorigenesis, glomerulonephritis, hyperphagia, and cholesterol biosynthesis, were shared among various inbred strains. These findings indicated that most rat strains harbored the disease-associated alleles and suggested that many unidentified functional polymorphisms might exist in inbred rat strains. The functional polymorphisms shared in inbred strains were also observed within outbred stocks available commercially. Therefore, this implies that experimental plans based on either rat inbred strains or outbred stocks need to be carefully designed with a full understanding of the genetic characteristics of the animals. To select the most suitable strains for experiments, the NBRP-Rat will periodically improve and update the genetic profiles of rat strains.

Functional genomics of the rat neuromedin U receptor 1 reveals a naturally occurring deleterious allele

“…Several functional polymorphisms in the rat genome have already been reported. A total of 16 functional polymorphisms linked to three coat color and 13 disease-associated genes in inbred rat strains have been characterized altogether with their allele frequencies in commercially available outbred stocks (22). Other examples of naturally occurring inactivating SNPs or gene insertion/deletion associated with marked phenotypic change have also been discovered in rat.…”

Role of Novel Rat-specific Fc Receptor in Macrophage Activation Associated with Crescentic Glomerulonephritis

“…We first investigated the distribution of Fcgr3-rs deletion throughout the rat phylogeny and found that the deletion was widespread. It was previously reported that five outbred Wistar and one Long-Evans stocks have Fcgr3-rs (23), suggesting that the deletion has originated from the ancestor outbred Wistar colony in the Wistar institute in the United States. We now confirm and extend these findings because all of the laboratory rat strains that we genotyped for Fcgr3 copy number variation are derived from outbred Wistar and Long-Evans stocks.…”

National BioResource Project-Rat and Related Activities

“…NBRP-Rat has recently surveyed 140 rat strains for gene mutations reported in particular rat strains that are responsible for functional polymorphisms (Fig. 3) [9]. Forty-nine rat strains show the insertion type of Cdkn1a/p21 [29], suggesting their resistance to prostate cancer; 79 rat strains have the duplication type of Fcgr3 [1], suggesting their resistance to experimentally induced nephritis; and 63 and 29 rat strains have point mutations of Lss and Fdft1 [17], respectively, suggesting their susceptibility to cataracts.…”

“…Such information is very helpful for selecting suitable rat strains for particular experiments. Since functional polymorphisms were also found in outbred or closed colonies at different rates among rat colonies [9], we recommend that testing or experiments with rats should be planned after giving careful consideration to this issue.…”