Golgi matrix protein gene, Golga3/Mea2, rearranged and re-expressed in pachytene spermatocytes restores spermatogenesis in the mouse.
In a transgenic mouse, Golga3/Mea2 gene (human homolog: GOLGA3/golgin-160) was disrupted by a translocation at the site of the transgene integration. Exons 8-24 of the disrupted gene remained intact and formed a fusion gene (DeltaMea2) with the antisense strand of E. coli-derived transgene by means of a cryptic splice signal in there. The protein product of DeltaMea2, virtually a form truncated to 2/3 of the normal size, localized to Golgi apparatus of pachytene spermatocytes and round spermatids. DeltaMea2 expression was specific to the testis, but varied among separate seminiferous tubules. It also showed variation among homozygous individuals from 0.5 to 4.3% of the wild type (wt) level. At the lowest levels, neither spermatids nor spermatozoa were present in the homozygous testes, but when the expression of DeltaMea2 increased to 4.3% of the wt level, high sperm production was restored and a sporadic (1/22) fertile homozygous male was obtained. The earliest apoptotic degeneration of pachytene spermatocytes evidenced at 17 dpp in homozygous testes in some discrete seminiferous tubules was preceded by DeltaMea2 expression in a variegated fashion at 16 dpp. These results consistently indicated that in homozygous testes, the pachytene spermatocytes which failed to express DeltaMea2 may undergo apoptotic degeneration. Golga3/Mea2, and DeltaMea2 in homozygotes, in a certain excessive amount may be important for survival of pachytene spermatocytes in the mouse.
Banu
Yasmin
Y
Kanagawa Cancer Center Research Institute, Nakao, Asahi-ku, Yokohama, Japan.
Matsuda
Miyuki
M
Yoshihara
Mitsuyo
M
Kondo
Masaaki
M
Sutou
Sizuyo
S
Matsukuma
Shoichi
S
D000818:Animals; D019677:Artificial Gene Fusion; D001324:Autoantigens; D001483:Base Sequence; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000378:metabolism; D006720:Homozygote; D007438:Introns / Q000235:genetics; D008297:Male; D008540:Meiosis / Q000235:genetics*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics; D012741:Sexual Maturation; D013090:Spermatocytes / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*
D001324:Autoantigens; C512726:Golga3 protein, mouse; C512727:MEA1 protein, human; C512728:Mea1 protein, mouse; D008565:Membrane Proteins; D011506:Proteins