Functional role for the c-Abl tyrosine kinase in meiosis I

Abstract

The c-Abl tyrosine kinase is activated by ionizing radiation and certain other DNA-damaging agents. The DNA-dependent protein kinase (DNA ± PK) and the ataxia telangiectasia mutated (ATM) gene product, e ectors in the DNA damage response, contribute to the induction of c-Abl activity. The present study demonstrates that c-Abl is expressed in mouse and rat testes, and predominantly in pachytene spermatocytes of meiosis I. The results also demonstrate that c-Abl interacts directly with meiotic chromosomes. In concert with a requirement for c-Abl at the pachytene stage, we show that, in contrast to wild-type mice, testes from Abl 7/7 mice exhibit defects in spermatogenesis. These ®ndings provide the ®rst demonstration that c-Abl plays a functional role in meiosis.

Role for c-Abl and p73 in the radiation response of male germ cells

“…However, only one of these bands, of approximately 115 kDa, remained after immunoprecipitation of c-Abl (Figures 2 and 3). A band of similar molecular weight has been described by Kharbanda et al, 1998 upon immunoprecipitation of c-Abl from isolated male rat germ cells (Kharbanda et al, 1998). In their paper, however, they do not show the c-Abl labelling pattern of total germ cell lysates.…”

“…While we only detected c-Abl in the cytoplasm, a nuclear localization of c-Abl has been described for isolated rat spermatocytes (Kharbanda et al, 1998). c-Abl contains both nuclear localization sequences (Wen et al, 1996) as well as a nuclear export sequence (Taagepera et al, 1998).…”

“…Interestingly, a testis speci®c c-abl mRNA was found in spermatids only (Meijer et al, 1987;Ponzetto and Wolgemuth, 1985) and we also found c-Abl expression in spermatids, although weak in comparison to other cell types. In c-Abl 7/7 mice, however, only few spermatids are formed (Kharbanda et al, 1998), indicating an indispensable function for c-Abl during meiosis or earlier in spermatogenesis.…”

Cycling, stressed-out and nervous: cellular functions of c-Abl

“…Interestingly, both knockout alleles resulted in the same phenotype: abl -/-mice are born runted, have shortened survival and exhibit abnormal eyes, frequent rectal prolapse and defective spermatogenesis 14 . Some animals also have splenic and thymic atrophy, with a 10-30-fold decrease in the number of mature B-and T-lymphocytes.…”

Comparison of mutated ABL1 and JAK2 as oncogenes and drug targets in myeloproliferative disorders

“…[29][30][31][32] Only 75% of ABL1 knockout mice survive the first week, 33 the remaining animals show severe defects in spermatogenesis, thymic and splenic atrophy, susceptibility to infections and reductions of T-and B-cell lymphocytes and their early precursors in lymphoid organs. [34][35][36] Surprisingly, the myeloerythroid system of these ABL1 mutants is normal. 37,38 Regulation of ABL1 activity appears to be particularly complex.…”