title: Reciprocal congenic lines for a major stroke QTL on rat chromosome 1.
abstract: We previously identified a quantitative trait locus (QTL) for stroke proneness between the kallikrein (Klk) and Mt1pa markers on rat chromosome 1. To gain functional insights, we constructed congenic strains by introgressing either the whole or selected chromosomal segments from the stroke-prone (SHRsp) onto the stroke-resistant (SHRsr) spontaneously hypertensive rat genome and vice versa. The phenotype was the latency to develop stroke under a Japanese high-salt, low-potassium diet for 3 mo [known as Japanese diet (JD)]. Blood pressure (BP) was measured by tail cuff throughout the experiment. Urinary protein excretion was monitored in all lines under JD. The SHRsp-derived lines carrying the SHRsr allele, and particularly the D1Rat134-Mt1pa chromosomal segment, had a significant delay of stroke occurrence and improved survival compared with SHRsp (P < 0.001). On the other hand, a significant occurrence of stroke events (20%) was detected in the reciprocal lines by the end of the 3-mo treatment with JD (P = 0.003). The stroke phenotype was also associated with increased proteinuria. Our results underscore the functional importance of the Chr 1 stroke QTL. Furthermore, they underscore the utility of stroke/congenic lines in dissecting the genetics of stroke.
authors.affiliation: Istituto di ricovero e cura a carattere scientifico Neuromed, Polo Molisano University La Sapienza, Pozzilli (Isernia), Italy. rubattu.speranza@neuromed.it
authors.forename: Speranza
authors.initials: S
authors.lastname: Rubattu
authors.forename: Norbert
authors.initials: N
authors.lastname: Hubner
authors.forename: Ursula
authors.initials: U
authors.lastname: Ganten
authors.forename: Anna
authors.initials: A
authors.lastname: Evangelista
authors.forename: Rosita
authors.initials: R
authors.lastname: Stanzione
authors.forename: Emanuele
authors.initials: E
authors.lastname: Di Angelantonio
authors.forename: Ralph
authors.initials: R
authors.lastname: Plehm
authors.forename: Reika
authors.initials: R
authors.lastname: Langanki
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gianazza
authors.forename: Luigi
authors.initials: L
authors.lastname: Sironi
authors.forename: Giulia
authors.initials: G
authors.lastname: D'Amati
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
mesh_terms: D000483:Alleles; D000818:Animals; D020296:Animals, Congenic / Q000235:genetics; D001794:Blood Pressure; D001835:Body Weight; D002545:Brain Ischemia / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000662:veterinary; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D008297:Male; D023421:Models, Animal; D017419:Potassium, Dietary / Q000008:administration & dosage; D011507:Proteinuria / Q000235:genetics / Q000662:veterinary; D040641:Quantitative Trait Loci; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*; D012376:Rodent Diseases / Q000235:genetics*; D017673:Sodium Chloride, Dietary / Q000633:toxicity; D020521:Stroke / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000662:veterinary*
chemical_list: D017419:Potassium, Dietary; D017673:Sodium Chloride, Dietary