Got1l1-KO Mouse

Got1l1, or glutamic-oxaloacetic transaminase-1 like 1, was initially proposed as a candidate enzyme for D-aspartate production. D-aspartate is an endogenous free amino acid with physiological roles in the brain, endocrine and exocrine tissues in mammals. The gene was thought to be involved in adult neurogenesis and potentially in the synthesis of D-aspartate from L-aspartate [1].

Studies using Got1l1 knockout (KO) mice found that Got1l1 mRNA is highly expressed in the testis but not in the brain and submandibular gland where D-aspartate is abundant. The D-aspartate contents in the testis and hippocampus of wild-type and Got1l1 KO mice were not significantly different. Recombinant Got1l1 expressed in mammalian cells showed L-aspartate aminotransferase activity but lacked aspartate racemase activity. Also, research on rat and human homologs of mouse GOT1L1 suggested they are not involved in D-aspartate biosynthesis [1,2]. Additionally, in T-cell acute lymphoblastic leukemia (T-ALL), the expression of GOT1L1 was significantly associated with shorter survival and was part of a 5-gene classifier for predicting high-risk forms of T-ALL [3]. In a case of malakoplakia, a rare urogenital tract inflammatory disease, a somatic gene mutation in GOT1L1 was detected, though its significance and relation to the disease are unclear [4].

In conclusion, Got1l1 does not seem to be the major aspartate racemase as initially hypothesized. Its role in D-aspartate biosynthesis remains uncertain. In the context of diseases, its expression is associated with high-risk T-ALL, and it was found mutated in a case of malakoplakia. The study of Got1l1 KO mouse models has been crucial in clarifying its limited role in D-aspartate production and may further help in understanding its implications in disease conditions like T-ALL and potentially malakoplakia.

References:

1. Tanaka-Hayashi, Ayumi, Hayashi, Shuuhei, Inoue, Ran, Yoshimura, Tohru, Mori, Hisashi. 2014. Is D-aspartate produced by glutamic-oxaloacetic transaminase-1 like 1 (Got1l1): a putative aspartate racemase? In Amino acids, 47, 79-86. doi:10.1007/s00726-014-1847-3. https://pubmed.ncbi.nlm.nih.gov/25287256/

2. Matsuda, Satsuki, Katane, Masumi, Maeda, Kazuhiro, Sekine, Masae, Homma, Hiroshi. 2015. Biosynthesis of D-aspartate in mammals: the rat and human homologs of mouse aspartate racemase are not responsible for the biosynthesis of D-aspartate. In Amino acids, 47, 975-85. doi:10.1007/s00726-015-1926-0. https://pubmed.ncbi.nlm.nih.gov/25646960/

3. Peng, Li-Jun, Zhou, Yue-Bo, Geng, Mei, Rousseaux, Sophie, Mi, Jian-Qing. 2022. Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemia. In BMC genomics, 23, 467. doi:10.1186/s12864-022-08688-1. https://pubmed.ncbi.nlm.nih.gov/35751016/

4. Zhang, Xiao-Ying, Li, Jun, Chen, Shui-Lian, Wang, Hao, He, Jin-Hua. 2023. Malakoplakia with aberrant ALK expression by immunohistochemistry: a case report. In Diagnostic pathology, 18, 97. doi:10.1186/s13000-023-01383-z. https://pubmed.ncbi.nlm.nih.gov/37644531/