Gene knockout analysis of two gamma-tubulin isoforms in mice

Gamma-tubulin regulates the nucleation of microtubules, but knowledge of its functions in vivo is still fragmentary. Here, we report the identification of two closely related gamma-tubulin isoforms, TUBG1 and TUBG2, in mice, and the generation of TUBG1- and TUBG2-deficient mice. TUBG1 was expressed ubiquitously, whereas TUBG2 was primarily detected in the brain. The development of TUBG1-deficient (Tubg1-/-) embryos stopped at the morula/blastocyst stages due to a characteristic mitotic arrest: the mitotic spindle was highly disorganized, and disorganized spindles showed one or two pole-like foci of bundled MTs that were surrounded by condensed chromosomes. TUBG2 was expressed in blastocysts, but could not rescue the TUBG1 deficiency. By contrast, TUBG2-deficient (Tubg2-/-) mice were born, grew, and intercrossed normally. In the brain of wild-type mice, TUBG2 was expressed in approximately the same amount as TUBG1, but no histological abnormalities were found in the Tubg2-/- brain. These findings indicated that TUBG1 and TUBG2 are not functionally equivalent in vivo, that TUBG1 corresponds to conventional gamma-tubulin, and that TUBG2 may have some unidentified function in the brain.