A single nucleotide mutation in Nppc is associated with a long bone abnormality in lbab mice.
BACKGROUND
The long bone abnormality (lbab) mouse is a new autosomal recessive mutant characterized by overall smaller body size with proportionate dwarfing of all organs and shorter long bones. Previous linkage analysis has located the lbab mutation on chromosome 1 between the markers D1Mit9 and D1Mit488.


RESULTS
A genome-based positional approach was used to identify a mutation associated with lbab disease. A total of 122 genes and expressed sequence tags at the lbab region were screened for possible mutation by using genomic DNA from lbabl/lbab, lbab/+, and +/+ B6 mice and high throughput temperature gradient capillary electrophoresis. A sequence difference was identified in one of the amplicons of gene Nppc between lbab/lbab and +/+ mice. One-step reverse transcriptase polymerase chain reaction was performed to validate the difference of Nppc in different types of mice at the mRNA level. The mutation of Nppc was unique in lbab/lbab mice among multiple mouse inbred strains. The mutation of Nppc is co-segregated with lbab disease in 200 progenies produced from heterozygous lbab/+ parents.


CONCLUSIONS
A single nucleotide mutation of Nppc is associated with dwarfism in lbab/lbab mice. Current genome information and technology allow us to efficiently identify single nucleotide mutations from roughly mapped disease loci. The lbab mouse is a useful model for hereditary human achondroplasia.
Jiao
Yan
Y
Departments of Orthopaedic Surgery--Campbell Clinic and Pathology, University of Tennessee Health Science Center, Memphis, Tennessee, USA. yjiao2@utmem.edu <yjiao2@utmem.edu>
Yan
Jian
J
Jiao
Feng
F
Yang
Hongbin
H
Donahue
Leah Rae
LR
Li
Xinmin
X
Roe
Bruce A
BA
Stuart
John
J
Gu
Weikuan
W
D000130:Achondroplasia / Q000235:genetics*; D000818:Animals; D009320:Atrial Natriuretic Factor; D049628:Body Size; D001842:Bone and Bones / Q000002:abnormalities*; D017931:DNA Primers; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D020098:Natriuretic Peptide, C-Type / Q000235:genetics*; D017354:Point Mutation; D011498:Protein Precursors / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D017931:DNA Primers; D005819:Genetic Markers; C431578:Nppa protein, mouse; D011498:Protein Precursors; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor