Structural and functional analysis of the ovine laminin receptor gene (RPSA): Possible involvement of the LRP/LR protein in scrapie response |
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Authors: | Ane Marcos-Carcavilla Jorge H Calvo Carmen González Carmen Serrano Katayoun Moazami-Goudarzi Pascal Laurent Maud Bertaud Hélène Hayes Anne E Beattie Jaber Lyahyai Inmaculada Martín-Burriel Juan María Torres Magdalena Serrano |
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Institution: | 1. Departamento de Mejora Genética Animal, INIA, Ctra La Coru?a Km 7.5, Madrid, 28040, Spain 2. Unidad de Tecnología en Producción Animal, Avda. Monta?ana 930, CITA, Zaragoza, 50059, Spain 5. Laboratorio de Genética Bioquímica, Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet 177, Zaragoza, 50013, Spain 3. Laboratoire de Génétique biochimique et de Cytogénétique, Département de Génétique Animale, INRA, Centre de Recherche de Jouy, Jouy-en-Josas, Cedex, 78352, France 4. AgResearch, Invermay Agricultural Centre, Private Bag 50034, Mosgiel, New Zealand 6. CISA-INIA, Carretera de Algete a El Casar s/n, Valdeolmos, Madrid, 28130, Spain
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Abstract: | 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. |
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