A de novo deafwaddler mutation of Pmca2 arising in ES cells and hitchhiking with
a targeted modification of the Pparg gene.
Authors Tsai YS, Pendse A, Moy SS, Mohri I, Perez A, Crawley JN, Suzuki K, Maeda N
Submitted By Nobuyo Maeda on 2/23/2009
Status Published
Journal Mammalian genome : official journal of the International Mammalian Genome Society
Year 2006
Date Published 7/1/2006
Volume : Pages 17(7) : 716 - 722
PubMed Reference 16845470
Abstract We observed severe ataxia in mice homozygous for modification of the Pparg
locus. Genetic analysis and nucleotide sequencing revealed that ataxia is caused
by a T692K substitution in plasma membrane calcium ATPase 2 (Pmca2), which is
tightly linked to Pparg, but not by modified PPARgamma itself. We traced this
mutation and found that it arose spontaneously during clonal expansion of the
targeted embryonic stem (ES) cells. Consistent with the deafwaddler phenotype in
other Pmca2 mutants, homozygous T692K Pmca2 mutants exhibit severe balance
disorder, impaired neurologic reflexes, and motor coordination, and have
profound hearing loss. Heterozygous mutants have normal movement and motor
function but are severely deficient in hearing. Our findings represent a
cautionary example since, although rare, spontaneous mutations do arise in ES
cells during culture and hitchhike onto the targeted gene mutation.

Investigators with authorship
Nobuyo MaedaUniversity of North Carolina


Atp2b2ATPase, Ca++ transporting, plasma membrane 2
Ppargperoxisome proliferator activated receptor gamma