Introduction

1. Reproductive Performance in Nucleotide Excision Repair (NER) Mouse Models: an Epidemiological Approach P.S. Tsai1, M. Nielen1, G.T.J. van der Horst2, B. Colenbrander1, J.A.P. Heesterbeek1 & J. M. Fentener van Vlissingen3 1Dept. Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University; 2Dept. Genetics and 3Erasmus Laboratory Animal Science Center (EDC), Erasmus University Medical Center, NL Material & Methods Introduction • Miceaged 2-9 months from 5 NER deficient mutant mouse models (genetic background: C57BL/6) Genetic modification may result in reduced reproductive performance, which either could be the direct phenotypic consequence of the genetic alteration (e.g. mutation, deletion) on reproductive physiology, or which could originate from decreased vitality, disturbed behavioral abnormalities or affected health. Aim • Epidemiological & Statistical tools To use epidemiological tools to explore, evaluate and to quantify reproductive performance of Nucleotide Excision Repair deficient (NER) mice as compared to control wild-type mice, based on data available from an in house AMS • ANOVA/ Kruskal Wallis H test, SPSS 10.0 • Analysis of covariance, ANCOVA, S-PLUS 6 • Univariable/ Multivariable Linear Regression, S-PLUS 6 • Poisson Regression, S-PLUS 6 • Post-hoc power analysis, Win Episcope 2.0 Results Table 1 Number of pups with genotype -/- from heterozygous couple. b c c c a b,d a a a a a Conclusions • Age effect (data not shown) • AMS database • Very useful for daily management. • Provides valuable information for epidemiological evaluations. • Can provide reliable information on reproductive performance when analyzed by epidemiological tools, even based on a small number of pairings. • Litter size decreased as parental age increased (from < 90 days to > 240days) suggesting premature aging related to DNA-repair deficiency. • Impaired reproduction in heterozygous mHR23B couples • reduced litter size ( 5.1 vs. 7.0 pups/ litter for wild type. fig.1) • prolonged pairing-to-birth interval ( 68.0 vs. 32.8 days for wild type. fig. 2) • 6.6-fold (13.25/ 2) lower number of mHR23B-/- pups than indicated by Mendelian expectation (table 1)