A male-sterile insertion in the mouse

Abstract

Is(7;l)40H was found in the daughter of a male mouse given spermatozoal X-irradiation. It is a non-inverted insertion of about half of chromosome 7 into chromosome 1, generating a long somatic marker chromosome. Breakpoints are in bands IB, 7B1, and 7F1; linkage tests show that these breakpoints are about midway between fz and In on the 1, and 0.2 units distal to ru-2 and 12 units proximal to fr on the 7. Female carriers had litters of about one-third normal size and showed some decline in length of reproductive life. Males were sterile, with testis weights only 30% of normal and with abrupt cessation of spermatogenesis in pachytene at stage IV of the seminiferous epithelial cycle. Positive sex-vesicle contact with the insertional configuration was found in only 40% of pachytene spermatocytes, which suggested that other factors may be involved in the spermatogonial breakdown. In oocytes at metaphase I 76% of insertion configurations were multivalent, because of one or more chiasmata in the inserted segment, as were 79% of synaptonemal complex configurations in male pachytenes. Karyotyping at 12.5 to 14.5 days of gestation showed that all embryos with duplications of the inserted segment were exencephalic, and the only example of a corresponding deficiency was retarded. Analysis of the consequences of heterozygosity for the insertion shows that the insertion length should be correlated with the frequency of unbalanced offspring and thus with the amount of F₁lethality. The genetic length of 36 cM estimated in this way from data on liveborn offspring is in reasonable agreement with estimates from cytological measurements and meiotic configurations but rather higher than that from linkage tests.

Mouse MutS-like protein Msh5 is required for proper chromosome synapsis in male and female meiosis

“…We speculate that at this stage of the seminiferous epithelium a pseudo G 2 /M checkpoint mechanism is operational for clearing the seminiferous tubule from incompetent meiotic cells. The same checkpoint mechanism may account for spermatocyte arrest in Is(7;1)40H heterozygotes (Searle et al 1983) and in Atm mice, which all correspond histologically with the pattern seen in Msh5-deficient mice, that is, death at stage IV (Xu et al 1996; T. Ashley, pers. comm.…”

Unpaired chromosomes at meiosis: cause or effect of gametogenic insufficiency?

“…1988a), which has a reduced sperm count, leading to sterility in som e m ale carriers: Is(7 ;l)4 0 H (Is40H ) (Searle et al. 1978(Searle et al. , 1983M ahadcvaiah et al.…”

Specific arrests of spermatogenesis in genetically modified and mutant mice

“…A complete and specific arrest at the level of pachytene spermatocytes in epithelial stage IV was first described in some cases of chromosomal aberrations (Searle et al, 1983;de Boer et al, 1986). Pairing problems of the aberrant chromosomes were thought to underlie the demise of these spermatocytes.…”