Pseudomyotonia in Romagnola cattle caused by novel ATP2A1 mutations
- Equal contributors
1 Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001, Bern, Switzerland
2 Department of Comparative Biomedicine and Food Safety, University of Padua, Viale dell’Università 16, 35020, Legnaro, Italy
3 Department of Veterinary Clinical Sciences, University of Padua, Viale dell’Università 16, 35020, Legnaro, Italy
4 IRCCS Istituto di Scienze Neurologiche, Via Altura 3, 40139 Bologna and Department of Neurological Sciences, University of Bologna, Bologna, Italy
5 Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano Emilia, Italy
BMC Veterinary Research 2012, 8:186 doi:10.1186/1746-6148-8-186Published: 9 October 2012
Bovine congenital pseudomyotonia (PMT) is an impairment of muscle relaxation induced by exercise preventing animals from performing rapid movements. Forms of recessively inherited PMT have been described in different cattle breeds caused by two independent mutations in ATP2A1 encoding a skeletal-muscle Ca2+-ATPase (SERCA1). We observed symptoms of congenital PMT in four related Romagnola beef cattle from Italy and evaluated SERCA1 activity and scanned ATP2A1 for possible causative mutations.
We obtained four PMT affected Romagnola cattle and noted striking clinical similarities to the previously described PMT cases in other cattle breeds. The affected animals had a reduced SERCA1 activity in the sarcoplasmic reticulum. A single affected animal was homozygous for a novel complex variant in ATP2A1 exon 8 (c.[632 G>T; 857 G>T]). Three out of four cases were compound heterozygous for the newly identified exon 8 variant and the exon 6 variant c.491 G>A(p. Arg146Gly), which has previously been shown to cause PMT in Chianina cattle. Pedigree analysis showed that the exon 8 double mutation event dates back to at least 1978. Both nucleotide substitutions are predicted to alter the SERCA1 amino acid sequence (p.[(Gly211Val; Gly284Val)]), affect highly conserved residues, in particular the actuator domain of SERCA1.
Clinical, biochemical and DNA analyses confirmed the initial hypothesis. We provide functional and genetic evidence that one novel and one previously described ATP2A1 mutation lead to a reduced SERCA1 activity in skeletal muscles and pseudomyotonia in affected Romagnola cattle. Selection against these mutations can now be used to eliminate the mutant alleles from the Romagnola breed.