RT Journal Article
T1 Fhl1 W122S causes loss of protein function and late-onset mild myopathy.
A1 Emmanuele, Valentina
A1 Kubota, Akatsuki
A1 Garcia Diaz, Beatriz
A1 Garone, Caterina
A1 Akman, Hasan O
A1 Sánchez-Gutiérrez, Daniel
A1 Escudero, Luis M.
A1 Kariya, Shingo
A1 Homma, Shunichi
A1 Tanji, Kurenai
A1 Quinzii, Catarina M.
A1 Hirano, Michio
K1 Músculos - Enfermedades
K1 Cromosomas humanos
K1 Miocardio
K1 Fenotipo
AB A member of the four-and-a-half-LIM (FHL) domain protein family, FHL1, is highly expressed in human adult skeletal and cardiac muscle. Mutations in FHL1 have been associated with diverse X-linked muscle diseases: scapuloperoneal (SP) myopathy, reducing body myopathy, X-linked myopathy with postural muscle atrophy, rigid spine syndrome (RSS) and Emery-Dreifuss muscular dystrophy. In 2008, we identified a missense mutation in the second LIM domain of FHL1 (c.365 G>C, p.W122S) in a family with SP myopathy. We generated a knock-in mouse model harboring the c.365 G>C Fhl1 mutation and investigated the effects of this mutation at three time points (3–5 months, 7–10 months and 18–20 months) in hemizygous male and heterozygous female mice. Survival was comparable in mutant and wild-type animals. We observed decreased forelimb strength and exercise capacity in adult hemizygous male mice starting from 7 to 10 months of age. Western blot analysis showed absence of Fhl1 in muscle at later stages. Thus, adult hemizygous male, but not heterozygous female, mice showed a slowly progressive phenotype similar to human patients with late-onset muscle weakness. In contrast to SP myopathy patients with the FHL1 W122S mutation, mutant mice did not manifest cytoplasmic inclusions (reducing bodies) in muscle. Because muscle weakness was evident prior to loss of Fhl1 protein and without reducing bodies, our findings indicate that loss of function is responsible for the myopathy in the Fhl1 W122S knock-in mice.
PB Oxford Academic
SN 0964-6906
YR 2014
FD 2014-09-30
LK https://hdl.handle.net/10630/33266
UL https://hdl.handle.net/10630/33266
LA eng
NO Valentina Emmanuele, Akatsuki Kubota, Beatriz Garcia-Diaz, Caterina Garone, Hasan O. Akman, Daniel Sánchez-Gutiérrez, Luis M. Escudero, Shingo Kariya, Shunichi Homma, Kurenai Tanji, Catarina M. Quinzii, Michio Hirano, Fhl1 W122S causes loss of protein function and late-onset mild myopathy, Human Molecular Genetics, Volume 24, Issue 3, 1 February 2015, Pages 714–726.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 4 mar 2026