title: The effect of DNA repair defects on reproductive performance in nucleotide excision repair (NER) mouse models: an epidemiological approach.
abstract: In this study, we used an epidemiological approach to analyze an animal database of DNA repair deficient mice on reproductive performance in five Nucleotide Excision Repair (NER) mutant mouse models on a C57BL/6 genetic background, namely CSA, CSB, XPA, XPC [models for the human DNA repair disorders Cockayne Syndrome (CS) and xeroderma pigmentosum (XP), respectively] and mHR23B (not associated with human disease). This approach allowed us to detect and quantify reproductive effects based on a relatively small number of matings. We measured and quantified the scale of the effect between factors that might influence reproductive performance (i.e. age at co-housing, seasons) and reproductive parameters (i.e. litter size and pairing-to-birth interval -'pbi'). Besides, we detected and quantified the differences in reproductive performance between wild type mice and heterozygous/homozygous NER mutant mice. From our analyses, we found impaired reproduction in heterozygous and homozygous knock out mice; in particular, reduced litter size and lengthened pbi was related to the NER mutation-mHR23B, in heterozygous couples, even if they were otherwise phenotypically normal. Heterozygous mHR23B couples produced a 6.6-fold lower number of mHR23B(-/-) pups than indicated by Mendelian expectation; other genetic deficiencies studied were not statistically significant from each other or wild type controls. We concluded that careful epidemiological evaluations by analysis of animal database could provide reliable information on reproductive performance and detect deviations that would remain unnoticed without this. Also, some managerial aspects of mouse breeding could be evaluated.
authors.affiliation: Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
authors.forename: P S
authors.initials: PS
authors.lastname: Tsai
authors.forename: M
authors.initials: M
authors.lastname: Nielen
authors.forename: G T J
authors.initials: GT
authors.lastname: van der Horst
authors.forename: B
authors.initials: B
authors.lastname: Colenbrander
authors.forename: J A P
authors.initials: JA
authors.lastname: Heesterbeek
authors.forename: J M Fentener
authors.initials: JM
authors.lastname: van Vlissingen
mesh_terms: D000818:Animals; D001947:Breeding; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D016021:Epidemiologic Studies; D005260:Female; D006801:Humans; D008098:Litter Size; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins / Q000235:genetics*; D012098:Reproduction / Q000502:physiology*; D012621:Seasons; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics*
chemical_list: C490652:Ckn1 protein, mouse; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins; C499250:Rad23b protein, mouse; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; C501002:Xpc protein, mouse; D004265:DNA Helicases; C078673:ERCC6 protein, human; C513075:Ercc6 protein, mouse; D045643:DNA Repair Enzymes