PMID- 35354714 OWN - NLM STAT- MEDLINE DCOM- 20220809 LR - 20220826 IS - 1881-7122 (Electronic) IS - 1341-1357 (Print) IS - 0007-5124 (Linking) VI - 71 IP - 3 DP - 2022 Aug 5 TI - A 3-Mbp fragment on rat chromosome 1 affects susceptibility both to stroke and kidney injury under salt loading in the stroke-prone spontaneously hypertensive rat: a genetic approach using multiple congenic strains. PG - 368-375 LID - 10.1538/expanim.21-0189 [doi] AB - We have previously reported that a major quantitative trait locus (QTL) responsible for susceptibility to salt-induced stroke in the stroke-prone spontaneously hypertensive rat (SHRSP) is located in a 3-Mbp region on chromosome 1 covered by SHRSP.SHR-(D1Rat23-D1Rat213)/Izm (termed Pr1.31), a congenic strain with segments from SHRSP/Izm introduced into the stroke-resistant SHR/Izm. Here, we attempted to narrow down the candidate region on chromosome 1 further through analyses of subcongenic strains constructed for the target region. Simultaneously, salt-induced kidney injury was evaluated through the measurement of urinary albumin and the gene expression of renal tubular injury markers (Kim-1 and Clu) to explore a possible mechanism leading to the onset of stroke. All subcongenic strains examined in this study showed lower susceptibility to salt-induced stroke than SHRSP. Interestingly, Pr1.31 had the lowest stroke susceptibility when compared with newly constructed subcongenic strains harboring fragments of the congenic sequence in Pr1.31. Although Kim-1 and Clu expression after 1 week of salt loading in Pr1.31 did not differ significantly from those in SHRSP, the urinary albumin level of Pr1.31 was significantly lower than those of the other subcongenic strains and that of SHRSP. The present results indicated that, although the congenic fragment in Pr1.31 harbored the gene(s) related to salt-induced organ damages, further genetic dissection of the candidate region was difficult due to multiple QTLs suggested in this region. Further analysis using Pr1.31 will unveil genetic and pathophysiological mechanisms underlying salt-induced end organ damages in SHRSP. FAU - Wang, Mei AU - Wang M AD - Department of Functional Pathology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan. AD - Graduate School, Ningxia Medical University, 1160 Shengli Street, Xingqing District, Yinchuan, Ningxia 750004, P.R. China. AD - Department of Cardiology, Shanghai Gongli Hospital, Second Military Medical University, 207 Juye Road, Pudong, Shanghai 200135, P.R. China. FAU - Ohara, Hiroki AU - Ohara H AD - Department of Functional Pathology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan. FAU - Egawa, Masahiro AU - Egawa M AD - Division of Nephrology, Shimane University Hospital, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan. FAU - Fukunaga, Shohei AU - Fukunaga S AD - Division of Nephrology, Shimane University Hospital, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan. FAU - Matsuo, Hiroyuki AU - Matsuo H AD - Department of Functional Pathology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan. AD - Department of Experimental Animals, Interdisciplinary Center for Science Research, Head Office for Research and Academic Information, Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan. FAU - Ge, Zhi-Ru AU - Ge ZR AD - Department of Cardiology, Shanghai Gongli Hospital, Second Military Medical University, 207 Juye Road, Pudong, Shanghai 200135, P.R. China. FAU - Nabika, Toru AU - Nabika T AD - Department of Functional Pathology, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan. LA - eng PT - Journal Article DEP - 20220329 PL - Japan TA - Exp Anim JT - Experimental animals JID - 9604830 RN - 0 (Albumins) RN - 0 (Sodium Chloride, Dietary) SB - IM MH - Albumins/adverse effects/genetics MH - Animals MH - Humans MH - *Hypertension/genetics MH - Kidney MH - Rats MH - Rats, Inbred SHR MH - *Sodium Chloride, Dietary/adverse effects MH - *Stroke/genetics PMC - PMC9388333 OTO - NOTNLM OT - congenic strain OT - quantitative trait loci (QTL) OT - spontaneously hypertensive rat (SHR) OT - stroke-prone SHR (SHRSP) COIS- The authors declare no conflicts of interest. EDAT- 2022/04/01 06:00 MHDA- 2022/08/10 06:00 PMCR- 2022/01/01 CRDT- 2022/03/31 05:11 PHST- 2022/04/01 06:00 [pubmed] PHST- 2022/08/10 06:00 [medline] PHST- 2022/03/31 05:11 [entrez] PHST- 2022/01/01 00:00 [pmc-release] AID - 21-0189 [pii] AID - 10.1538/expanim.21-0189 [doi] PST - ppublish SO - Exp Anim. 2022 Aug 5;71(3):368-375. doi: 10.1538/expanim.21-0189. Epub 2022 Mar 29.