Fig. 1.

Design and the founders of Jcl: SD Brca2 (Here only Brca2 to be italic, please) mutant rats harboring a frameshift on exon 11 with embryonic lethality in the homozygotes. (a) Structure of rat BRCA2 protein. (b) Structure of rat Brca2 and guide RNA used for genome editing. (c-e) The pedigree of founder rats. (f) A graphical summary of the inheritance rate of the mutant Brca2 allele in the F1 generation, categorized by the site of the mutated amino acid. Founder rats that produced no pups are also plotted as 0%. This figure indicates that the frameshift mutation in Brca2 is less likely to be inherited to the subsequent generation. (g) The nucleotide sequence of the modified region within the Brca2 gene and their notation. (h) Representative result of genotyping PCR of the Brca2^wt/wt and Brca2^wt/mut. (i) Contingency table showing observed and expected counts of offspring with each genotype from 4 pairs of Brca2^wt/mut male rats and Brca2^wt/mut female rats. (j) Macroscopic image of uteri from a pregnant female taken at GD 8.5. Arrow heads, conceptuses; arrows, malformed conceptuses. (k, l) Representative histology of dying conceptuses (k) and live conceptuses (l) at GD 8.5 (arrows, embryonic components; bar = 200 μm). In the dying conceptus, cell detachment, loss of tissue continuity and hemorrhage are observed. (m) Microscopic image showing remnant of pregnancy observed at GD 12.5 (arrow heads, trophoblastic cells; bar = 200 μm). Fetal components are absent, and cluster of trophoblastic cells with large nuclei, some of which are syncytialized, are observed.