The Founder Strains of the Collaborative Cross Express a Complex Combination of Advantageous and Deleterious Traits for Male Reproduction.
Surveys of inbred strains of mice are standard approaches to determine the heritability and range of phenotypic variation for biomedical traits. In addition, they may lead to the identification of novel phenotypes and models of human disease. Surprisingly, male reproductive phenotypes are among the least-represented traits in the Mouse Phenome Database. Here we report the results of a broad survey of the eight founder inbred strains of both the Collaborative Cross (CC) and the Diversity Outbred populations, two new mouse resources that are being used as platforms for systems genetics and sources of mouse models of human diseases. Our survey includes representatives of the three main subspecies of the house mice and a mix of classical and wild-derived inbred strains. In addition to standard staples of male reproductive phenotyping such as reproductive organ weights, sperm counts, and sperm morphology, our survey includes sperm motility and the first detailed survey of testis histology. As expected for such a broad survey, heritability varies widely among traits. We conclude that although all eight inbred strains are fertile, most display a mix of advantageous and deleterious male reproductive traits. The CAST/EiJ strain is an outlier, with an unusual combination of deleterious male reproductive traits including low sperm counts, high levels of morphologically abnormal sperm, and poor motility. In contrast, sperm from the PWK/PhJ and WSB/EiJ strains had the greatest percentages of normal morphology and vigorous motility. Finally, we report an abnormal testis phenotype that is highly heritable and restricted to the WSB/EiJ strain. This phenotype is characterized by the presence of a large, but variable, number of vacuoles in at least 10% of the seminiferous tubules. The onset of the phenotype between 2 and 3 wk of age is temporally correlated with the formation of the blood-testis barrier. We speculate that this phenotype may play a role in high rates of extinction in the CC project and in the phenotypes associated with speciation in genetic crosses that use the WSB/EiJ strain as representative of the Mus muculus domesticus subspecies.
Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, North Carolina 27599.
Fanny
F
Odet
Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, North Carolina 27599.
Wenqi
W
Pan
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599.
Timothy A
TA
Bell
Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, North Carolina 27599.
Summer G
SG
Goodson
Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, North Carolina 27599.
Alicia M
AM
Stevans
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599.
Zianing
Z
Yun
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695.
David L
DL
Aylor
Department of Computer Science, University of North Carolina, Chapel Hill, North Carolina 27599.
Chia-Yu
CY
Kao
Department of Computer Science, University of North Carolina, Chapel Hill, North Carolina 27599.
Leonard
L
McMillan
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599 dao@med.unc.edu fernando@med.unc.edu.
Fernando Pardo-Manuel
FP
de Villena
Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, North Carolina 27599 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599 dao@med.unc.edu fernando@med.unc.edu.
Deborah A
DA
O'Brien
D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D018703:Founder Effect; D007248:Infertility, Male / Q000235:genetics; D019344:Lactic Acid / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D012098:Reproduction / Q000235:genetics*; D013076:Sperm Count; D013081:Sperm Motility; D013094:Spermatozoa / Q000166:cytology / Q000502:physiology; D013737:Testis / Q000033:anatomy & histology / Q000166:cytology / Q000502:physiology
D019344:Lactic Acid
Collaborative Cross; motility; sperm; vacuole