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Analyzing Complex Polygenic Traits
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Bernard R. Lauwerys, Edward K. Wakeland
Other candidate genes have been identified in the subcongenic intervals and the effects of SNPs on their expression and function are being thoroughly evaluated. Again, these differences do not constitute definitive evidence for involvement in disease pathogenesis. Final demonstration for establishing the pathogenic role of a candidate gene requires that its correction results in suppression of the compound phenotype present in the congenic strains. This can be achieved in transgenic approaches, using either conventional or BAC transgenes. While conventional transgenesis induces dramatic overexpression of the gene, BAC transgenes contain much larger segments of genomic DNA, also including normal regulatory sequences, thereby resulting in physiological levels of protein expression (for review, see ref. 77).
Hormonal and Nonhormonal Mechanisms of Sexual Differentiation of the Zebra Finch Brain: Embracing the Null Hypothesis
Published in Akira Matsumoto, Sexual Differentiation of the Brain, 2017
Some experiments have manipulated the composition of genes on the Y chromosome in order to examine their effects on behavior. For example, aggressive behavior in mice differs across strains. Maxson and co-workers89–91 have produced inbred congenic strains that differ in their Y chromosome but otherwise have the same autosomal background. Males of these congenic strains show different levels of aggressive behavior, a result that indicates that some Y genes influence aggression. These Y genes are candidates for direct genetic influences on aggressive behavior, which is a sexually dimorphic trait. However, the between-strain differences are also potentially attributable to Y effects on the level of androgens or the sensitivity of neural circuits to gonadal hormones. In the end, one can only determine if a specific action of a gene has a direct, nonhormonal effect on neural development by identifying the gene and establishing its molecular and cellular mechanism of action. If the gene is expressed in brain in appropriate places and at appropriate times of development, and manipulation of the gene product alters the course of sexual differentiation, one can build a case for a nonhormonal mechanism of action.
Dictionary
Published in Mario P. Iturralde, Dictionary and Handbook of Nuclear Medicine and Clinical Imaging, 1990
Congenic. (Originally called congenic resistant) Denotes a line of mice identical or nearly identical with other inbred strains except for the substitution at one histocompatibility locus of a foreign allele introduced by appropriate crosses with a second inbred strain.
Animal models of systemic lupus erythematosus and their applications in drug discovery
Published in Expert Opinion on Drug Discovery, 2022
Yue Xin, Bo Zhang, Junpeng Zhao, Qianmei Liu, Haoyuan Yin, Qianjin Lu
Based on the polygenic mechanism of SLE, several murine models have been constructed through the modification of the specific genes in wild-type mice, usually B6. Two main categories of genetically modified models have been developed: knockout or transgenic models and spontaneous mouse-derived congenic models. In the knockout or transgenic model, tolerance is disrupted by modifying some critical immunological processes, including enhancing the immunogenicity of apoptotic debris (C1qa−/−, DNase I−/−, and Tlr7 Tg, Tir8−/−), altering lymphocyte signaling (Fcgr2b−/−, Cd22−/−, Cd19 Tg, Lyn−/−), or prolonging the lifespan of autoreactive lymphocytes (Bim−/−, Bcl-2 Tg, and Ctla-4−/−), in which the B6.Tlr7.Tg and B6.Fcgr2b−/− mice are the mostly commonly used [66–68]. For the congenic model, the gene fragments containing one or a cluster of susceptible loci, which are derived from the lupus-prone strain, are integrated into the nonlupus-prone strain to induce a lupus-like disease. As mentioned above, these loci include NZB-derived Nba2 and Nba5, NZM 2410-derived Sle123, NZM 2328-derived Cgnz1 and Agnz1, MRL/lpr-derived Mag and Lmb3, and BXSB-derived Bxs 1–6 loci [69].
Pathophysiological significance of Stim1 mutation in sympathetic response to stress and cardiovascular phenotypes in SHRSP/Izm: In vivo evaluation by creation of a novel gene knock-in rat using CRISPR/Cas9
Published in Clinical and Experimental Hypertension, 2021
Batbayar Odongoo, Hiroki Ohara, Davis Ngarashi, Takehito Kaneko, Yayoi Kunihiro, Tomoji Mashimo, Toru Nabika
Quantitative trait locus (QTL) analysis and construction of congenic strains have been widely used as a set of genetic approaches for identifying genes associated with cardiovascular traits in hypertensive rats (15). We previously showed that a major BP QTL existed in rat chromosome (chr) 1 through a genome-wide linkage analysis using F2 generation cross derived from SHRSP and normotensive Wistar-Kyoto (WKY) rats (16). Then, we created reciprocal congenic lines between SHRSP and WKY for the BP QTL on chr1 and revealed that the chr1 QTL was implicated in the pathophysiology of exaggerated sympathetic response to stress in SHRSP (17–19) with possible involvement of hyperactivity of the RVLM (20). Subcongenic analysis successfully narrowed down the candidate region to a 1.2 Mbp fragment on the chr1 QTL, finally, stromal interaction molecule 1 (Stim1) was identified as the most promising candidate gene responsible for the sympatho-excitation to stress in SHRSP according to the existence of a nonsense mutation (c.1918 C > T, p.Arg640X) in this gene resulting in the truncated STIM1 expression in SHRSP (21).
Vasculitis and crescentic glomerulonephritis in a newly established congenic mouse strain derived from ANCA-associated vasculitis-prone SCG/Kj mice
Published in Autoimmunity, 2019
Yoshitomo Hamano, Fuyu Ito, Osamu Suzuki, Minako Koura, Shuji Matsuoka, Toshiyuki Kobayashi, Yoshinobu Sugitani, Nadila Wali, Ai Koyanagi, Okio Hino, Shoichi Suzuki, Ryuichi Sugamata, Hiromichi Yoshizawa, Wako Yumura, Naoki Maruyama, Yosuke Kameoka, Yoshihiro Noda, Yasuko Hasegawa, Tomio Arai, Kazuo Suzuki
The internal and terminal markers of the congenic intervals were mapped with polymorphic SSRs (Figure 1(B)) [11]. Regarding the centromeric end, the end of the SCG/Kj interval was between D1MIT134 and D1MIT11. D1MIT11 was the most centromeric marker of Scg-2/Man-1 [11]. Regarding the telomeric end, the SCG/Kj interval extended approximately 2 cM telomeric of D1MIT166, the most telomeric marker of the Scg-1 interval. There was a chromosomal segment of approximately 13 cM between the telomeric end of Scg-2/Man-1 and the centromeric end of Scg-1. We investigated the origin of this segment using two markers, D1MIT30 and D1MIT102. The genotypes of these two markers were both homozygous for SCG/Kj. Taken together, the congenic interval introduced from SCG/Kj consisted of an approximately 36-cM chromosomal segment that included the intervals of Scg-1 and Scg-2/Man-1 at the telomeric and centromeric ends, respectively (Figure 1(B)).