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Golgi matrix protein gene, Golga3 / Mea2 , rearranged and re‐expressed in pachytene spermatocytes restores spermatogenesis in the mouse
Author(s) -
Banu Yasmin,
Matsuda Miyuki,
Yoshihara Mitsuyo,
Kondo Masaaki,
Sutou Sizuyo,
Matsukuma Shoichi
Publication year - 2002
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.10035
Subject(s) - biology , spermatogenesis , transgene , gene , exon , chromosomal translocation , spermatocyte , genetically modified mouse , testicle , fusion gene , microbiology and biotechnology , andrology , genetics , endocrinology , meiosis , medicine
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 (Δ Mea2 ) with the antisense strand of E. coli ‐derived transgene by means of a cryptic splice signal in there. The protein product of Δ Mea2 , virtually a form truncated to 2/3 of the normal size, localized to Golgi apparatus of pachytene spermatocytes and round spermatids. Δ Mea2 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 Δ Mea2 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 Δ Mea2 expression in a variegated fashion at 16 dpp. These results consistently indicated that in homozygous testes, the pachytene spermatocytes which failed to express Δ Mea2 may undergo apoptotic degeneration. Golga3/Mea2, and ΔMea2 in homozygotes, in a certain excessive amount may be important for survival of pachytene spermatocytes in the mouse. Mol. Reprod. Dev. 61: 288–301, 2002. © 2002 Wiley‐Liss, Inc.