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Anamizu, Y. et al.

Klotho insufficiency causes decrease of ribosomal RNA gene transcription activity, cytoplasmic RNA and rough ER in the spinal anterior horn cells.

The klotho gene was identified in 1997 as the gene whose severe insufficiency (kl/kl) causes a syndrome resembling human aging, such as osteoporosis, arteriosclerosis, gonadal atrophy, emphysema, and short life span in a mouse strain. Regarding the gait disturbance reported in kl/kl mice, the present study examined the spinal cord of kl/kl mice, and revealed decreases in the number of large anterior horn cells (AHCs), the amount of cytoplasmic RNA, the number of ribosomes and rough endoplasmic reticulum (rER), and the activity of ribosomal (r) RNA gene transcription without significant loss of the total number of neurons in the ventral gray matter. Increased immunostaining of phosphorylated neurofilament in the AHCs and of glial fibrillary acidic protein in reactive astrocytes in the anterior horn of kl/kl mice were also observed. On the other hand, the posterior horn was quite well preserved. The results suggest that the kl/kl insufficiency causes atrophy and dysfunction of the spinal AHCs through decreased activity of rRNA gene transcription, which may reduce the amount of cytoplasmic RNA and the number of ribosomes and rER. These findings resemble those found in the spinal cord of patients with classic amyotrophic lateral sclerosis (ALS). The results show that klotho gene insufficiency causes dysfunction of the protein synthesizing system in the AHCs, and might indicate the klotho gene is involved in the pathological mechanism of classic ALS. The kl/kl is a new animal model of AHC degeneration, and may provide clues to understanding the etiology of classic ALS.[1]

References

Klotho insufficiency causes decrease of ribosomal RNA gene transcription activity, cytoplasmic RNA and rough ER in the spinal anterior horn cells. Anamizu, Y., Kawaguchi, H., Seichi, A., Yamaguchi, S., Kawakami, E., Kanda, N., Matsubara, S., Kuro-o, M., Nabeshima, Y., Nakamura, K., Oyanagi, K. Acta Neuropathol. (2005) [Pubmed]

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