A single nucleotide mutation in <it>Nppc </it>is associated with a long bone abnormality in <it>lbab </it>mice

• Main Authors: Roe Bruce A, Li Xinmin, Donahue Leah, Yang HongBin, Yan Jian, Jiao Feng, Jiao Yan, Stuart John, Gu Weikuan
• Format: Article
• Language: English
• Published: BMC 2007-04-01
• Series: BMC Genetics
• Online Access: http://www.biomedcentral.com/1471-2156/8/16

<p>Abstract</p> <p>Background</p> <p>The long bone abnormality (<it>lbab</it>) 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 <it>lbab </it>mutation on chromosome 1 between the markers <it>D1Mit9 </it>and <it>D1Mit488</it>.</p> <p>Results</p> <p>A genome-based positional approach was used to identify a mutation associated with <it>lbab </it>disease. A total of 122 genes and expressed sequence tags at the <it>lbab </it>region were screened for possible mutation by using genomic DNA from <it>lbabl/lbab, lbab</it>/+, and +/+ B6 mice and high throughput temperature gradient capillary electrophoresis. A sequence difference was identified in one of the amplicons of gene <it>Nppc </it>between <it>lbab/lbab </it>and +/+ mice. One-step reverse transcriptase polymerase chain reaction was performed to validate the difference of <it>Nppc </it>in different types of mice at the mRNA level. The mutation of <it>Nppc </it>was unique in <it>lbab/lbab </it>mice among multiple mouse inbred strains. The mutation of <it>Nppc </it>is co-segregated with <it>lbab </it>disease in 200 progenies produced from heterozygous <it>lbab</it>/+ parents.</p> <p>Conclusion</p> <p>A single nucleotide mutation of <it>Nppc </it>is associated with dwarfism in <it>lbab/lbab </it>mice. Current genome information and technology allow us to efficiently identify single nucleotide mutations from roughly mapped disease loci. The <it>lbab </it>mouse is a useful model for hereditary human achondroplasia.</p>