Arrest of spermatogenesis and defective breast development in mice lacking A-myb

Abstract

The Myb gene family currently consists of three members, named A-, B- and c-myb. These genes encode nuclear proteins that bind DNA in a sequence-specific manner and function as regulators of transcription. In adult male mice, A-myb is expressed predominantly in male germ cells. In female mice, A-myb is expressed in breast ductal epithelium, mainly during pregnancy-induced ductal branching and alveolar development. We report here that mice homozygous for a germline mutation in A-myb develop to term but show defects in growth after birth and male infertility due to a block in spermatogenesis. Morphological examination of the testes of A-myb-/- males revealed that the germ cells enter meiotic prophase and arrest at pachytene. In adult homozygous null A-myb female mice, the breast epithelial compartment showed underdevelopment of breast tissue following pregnancy and the female mice were unable to nurse their newborn pups. These results demonstrate that A-myb plays a critical role in spermatogenesis and mammary gland development.

Analysis of the gene expression profile of mouse male meiotic germ cells

“…Many of these genes encode proteins specifically involved in the control of the meiotic cell cycle, such as cyclin A1 (Table 2) (Liu et al, 1998), cdk4-inhibitors p18 and p19 (Table 2) (Zindy et al, 2001), A-myb (Table 2) (Toscani et al, 1997), Nek2 (Table 9) (Di Agostino et al, 2002), but in many cases their expression reflects meiotic accumulation of transcripts destined to be translated later during spermiogenesis, such as testis-specific lactate dehydrogenase (Table 7) (Li et al, 1998), testis-specific poly(A) polymerase b (Table 8) Kashiwabara et al, 2002), calmegin (Table 9) (Ikawa et al, 1997), preproacrosin (Table 5) (Kremling et al, 1991), fertilin b (Table 5) (Cho et al, 1998), Trf2 (Table 3) (Martianov et al, 2001), MSJ-1 (Table 5) (Berruti and Martegani, 2001), Tpx1 (Table 5) (Kasahara et al, 1989), Tekt1 (Table 5) (Larsson et al, 2000), Tesp1 (Table 5) (Kohno et al, 1998) and so on. It is noteworthy that the spermatocyte-specific expression of a large number of genes encoding enzymes is involved in glycolysis and gluconeogenesis, beside that of Pgk2, encoding a well known meiotic isoform of phosphoglycerate kinase (Boer et al, 1987) (Table 7).…”

AATYK: A novel tyrosine kinase induced during growth arrest and apoptosis of myeloid cells

“…Normal mouse brain whole cell lysates were prepared as previously described (Toscani et al, 1997). For Western blot analysis, 100 mg of whole cell lysate were separated by SDS ± PAGE (6%) and transferred to a nitrocellulose membrane and probed with an AATYK-speci®c polyclonal antiserum.…”

Diverse developing mouse lineages exhibit high-level c-Myb expression in immature cells and loss of expression upon differentiation

“…There are both distinct and overlapping sites of expression. A-myb knockout mice have defects in late stage spermatogenesis and mammary gland development (Toscani et al, 1997;Trauth et al, 1994). B-myb, expressed widely during embryogenesis (Sitzmann et al, 1996) and present in earlier stages of testes development, is also strongly down-regulated upon terminal di erentiation (Latham et al, 1996).…”