A spontaneous smc1b mutation causes cohesin protein dysfunction and sterility in mice

In this paper, we describe a novel spontaneous mutation of the Smc1b gene coding a cohesin component, which causes female and male sterility. We have discovered an ICR male mouse with a novel autosomal recessive gene that causes small gonads and sterility in both sexes. Mutant female and male mice homozygous for the novel sterility gene had normal body weights and showed normal mating behavior, but did not produce any offspring. Histological examination showed that Sertoli cells and spermatogonia were present in the testicular seminiferous tubules in 8-week-old mutant male mice, but no spermatids or spermatozoa were observed. Mutant females showed a markedly reduced number of oocytes with age. The novel sterility gene mapped between D15Mit105 (47.9 cM) and D15Mit171 (54.5 cM) on chromosome 15. Sequences of three candidate sterility genes, Dmc1, Mei1 and Smc1b, which are closely linked to these microsatellite markers, were compared between normal and mutant mice. The Dmc1 and Mei1 genes showed the same sequences in both normal and mutant mice, but the Smc1b gene had a deletion of 16 nucleotides in exon 5, in the mutant mice. We concluded that this deletion led to a frame-shift, which generated a stop codon at position 761 (amino acid 247) of the Smc1b cDNA in mutant mice.