Structural and functional analysis of the ovine laminin receptor gene (RPSA): Possible involvement of the LRP/LR protein in scrapie response.
Scrapie is a prion disease affecting sheep and goats. Susceptibility to this neurodegenerative disease shows polygenic variance. The involvement of the laminin receptor (LRP/LR) in the metabolism and propagation of prions has previously been demonstrated. In the present work, the ovine laminin receptor gene (RPSA) was isolated, characterized, and mapped to ovine chromosome OAR19q13. Real-time RT-PCR revealed a significant decrease in RPSA mRNA in cerebellum after scrapie infection. Conversely, no differences were detected in other brain regions such as diencephalon and medulla oblongata. Association analysis showed that a polymorphism reflecting the presence of a RPSA pseudogene was overrepresented in a group of sheep resistant to scrapie infection. No amino acid change in the LRP/LR protein was found in the 126 sheep analyzed. However, interesting amino acid positions (241, 272, and 290), which could participate in the species barrier to scrapie and maybe to other transmissible spongiform encephalopathies, were identified by comparing LRP/LR sequences from various mammals with variable levels of resistance to scrapie.
Marcos-Carcavilla
Ane
A
Departamento de Mejora Genética Animal, INIA, Ctra La Coruña Km 7.5, Madrid, 28040, Spain. amarcos@inia.es
Calvo
Jorge H
JH
González
Carmen
C
Serrano
Carmen
C
Moazami-Goudarzi
Katayoun
K
Laurent
Pascal
P
Bertaud
Maud
M
Hayes
Hélène
H
Beattie
Anne E
AE
Lyahyai
Jaber
J
Martín-Burriel
Inmaculada
I
Torres
Juan María
JM
Serrano
Magdalena
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics; D005786:Gene Expression Regulation; D005838:Genotype; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017474:Receptors, Laminin / Q000737:chemistry* / Q000235:genetics*; D012608:Scrapie / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D034561:Sheep, Domestic / Q000235:genetics*
D017474:Receptors, Laminin