Abstract:
Congenital pseudo-myotonia (PMT) in Chianina cattle
is a muscle function disorder which is mainly
characterized by an exercise-induced muscle
contracture which prevents animals from performing
muscular activities more intense than a simple walk at
a slow pace. Mutations in the human ATP2A1 gene,
encoding a fast-twitch skeletal-muscle Ca2+ ATPase
(SERCA1), cause Brody myopathy, a very similar rare
autosomal recessive disorder characterized by
exercise-induced muscle cramps and impaired muscle
relaxation. The analysis of the collected Chianina
pedigree data suggested monogenic autosomal
recessive inheritance and revealed that all PMT
affected individuals traced back to a single founder
sire. A family with 16 PMT affected cattle was
genotyped with two bovine ATP2A1 gene flanking
microsatellites.Linkage analysis within this family
showed that the PMT mutation could be assigned to
the ATP2A1 gene region on BTA25 (LOD score >3).
Subsequent DNA sequencing of the 16 PMT affected
calves revealed a missense mutation (c.491G>A)
leading to a p.Arg164His substitution in exon 6 of
ATP2A1. Arg164 in bovine ATP2A1 is located within
the functional important N-terminal actuator domain
and is a highly conserved residue. Genotyping 112
unaffected unrelated Chianina animals did not reveal a
single individual homozygous for mutation and
indicated a carrier frequency of >0.10