Abstract
BackgroundPreterm birth is an enormous public health problem, affecting over 12% of live births and costing over $26 billion in the United States alone. The causes are complex, but twin studies support the role of genetics in determining gestation length. Despite widespread use of the mouse in studies of the genetics of preterm birth, there have been few studies that actually address the precise natural gestation length of the mouse, and to what degree the timing of labor and birth is genetically determined.Methodology/Principal FindingsTo further develop the mouse as a genetic model of preterm birth, we developed a high-throughput monitoring system and measured the gestation length in 15 inbred strains. Our results show an unexpectedly wide variation in overall gestation length between strains that approaches two full days, while intra-strain variation is quite low. Although litter size shows a strong inverse correlation with gestation length, genetic difference alone accounts for a significant portion of the variation. In addition, ovarian transplant experiments support a primary role of maternal genetics in the determination of gestation length. Preliminary analysis of gestation length in the C57BL/6J-Chr#A/J/NaJ chromosome substitution strain (B.A CSS) panel suggests complex genetic control of gestation length.Conclusions/SignificanceTogether, these data support the role of genetics in regulating gestation length and present the mouse as an important tool for the discovery of genes governing preterm birth.
Highlights
More than 12% of infants are born prematurely and suffer a high degree of morbidity and mortality
Our data clearly indicate that genetic background plays a major role in determining gestation length, and supports the use of mice to study the genetic regulation of preterm birth
Given the large difference between C57BL/6J and 129S1/SvImJ, this information is relevant to investigators utilizing knockout models, which are frequently maintained on segregating backgrounds, to understand mechanisms that govern preterm birth [3,4,9]
Summary
More than 12% of infants are born prematurely and suffer a high degree of morbidity and mortality (www.marchofdimes. com/peristats/). Twin and association studies in humans have demonstrated that there is a strong genetic contribution to the determination of gestation time, but specific causative genes have not been identified [2]. One critical gap in our understanding is the precise gestation length (GL) of the mouse, generally thought to be between 18 and 22 days. It is not clear if this range represents intra- or inter-strain variability, if reported differences in gestation time are dependent of litter size, or if length of gestation affects pup survival. Despite widespread use of the mouse in studies of the genetics of preterm birth, there have been few studies that address the precise natural gestation length of the mouse, and to what degree the timing of labor and birth is genetically determined
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