Limits...
Overexpression of the mitochondrial methyltransferase TFB1M in the mouse does not impact mitoribosomal methylation status or hearing.

Lee S, Rose S, Metodiev MD, Becker L, Vernaleken A, Klopstock T, Gailus-Durner V, Fuchs H, Hrabě De Angelis M, Douthwaite S, Larsson NG - Hum. Mol. Genet. (2015)

Bottom Line: Non-syndromic deafness and predisposition to aminoglycoside-induced deafness can be caused by specific mutations in the 12S rRNA gene of mtDNA and are thus maternally inherited traits.In contrast, it was recently reported that signaling induced by 'hypermethylation' of two conserved adenosines of 12S rRNA in the mitoribosome is of key pathophysiological importance in sensorineural deafness.We thus conclude that therapies directed against mitoribosomal methylation are unlikely to be beneficial to patients with sensorineural hearing loss or other types of mitochondrial disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden.

No MeSH data available.


Related in: MedlinePlus

Normal ABRs in BAC-TFB1M transgenic mice. The ABRs of control (WT, blue lines) and BAC-TFB1M transgenic (C7.1, red lines) mice are shown. The hearing sensitivity of control and transgenic mice was assessed by measuring ABR after different auditory stimuli. Stimulus intensity thresholds were measured at different frequencies. The medians and quartiles are shown. Male (A) and female (B) mice were analyzed at 4, 7, and 9 months of age. Error bars represent ±SD.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4664167&req=5

DDV427F5: Normal ABRs in BAC-TFB1M transgenic mice. The ABRs of control (WT, blue lines) and BAC-TFB1M transgenic (C7.1, red lines) mice are shown. The hearing sensitivity of control and transgenic mice was assessed by measuring ABR after different auditory stimuli. Stimulus intensity thresholds were measured at different frequencies. The medians and quartiles are shown. Male (A) and female (B) mice were analyzed at 4, 7, and 9 months of age. Error bars represent ±SD.

Mentions: We attempted to confirm the report that the Tg-mtTFB1 mice have higher auditory brainstem response (ABR) thresholds across the entire range of frequencies at 3–6 months of age (30). We investigated hearing in BAC-TFB1M (C7.1) mice, after establishing that they overexpress TFB1M to the same extent as Tg-mtTFB1 mice (Fig. 4C and D). Male (Fig. 5A) and female (Fig. 5B) BAC-TFB1M and wild-type mice aged 4 months showed very similar ABRs. However, a subtle, but statistically significant, elevation in ABR thresholds for click ABR and at 24 kHz was seen in female mice of this age (Fig. 5B). ABR measurements were therefore carried out on slightly older mice at 7 and 9 months and revealed no additional difference between BAC-TFB1M and wild-type mice of either sex (Fig. 5A and B). An increase in hearing thresholds at higher frequencies was to be expected, together with a general age-related decline in hearing but, importantly, the TFB1M genotype had no influence on this phenomenon.Figure 5.


Overexpression of the mitochondrial methyltransferase TFB1M in the mouse does not impact mitoribosomal methylation status or hearing.

Lee S, Rose S, Metodiev MD, Becker L, Vernaleken A, Klopstock T, Gailus-Durner V, Fuchs H, Hrabě De Angelis M, Douthwaite S, Larsson NG - Hum. Mol. Genet. (2015)

Normal ABRs in BAC-TFB1M transgenic mice. The ABRs of control (WT, blue lines) and BAC-TFB1M transgenic (C7.1, red lines) mice are shown. The hearing sensitivity of control and transgenic mice was assessed by measuring ABR after different auditory stimuli. Stimulus intensity thresholds were measured at different frequencies. The medians and quartiles are shown. Male (A) and female (B) mice were analyzed at 4, 7, and 9 months of age. Error bars represent ±SD.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664167&req=5

DDV427F5: Normal ABRs in BAC-TFB1M transgenic mice. The ABRs of control (WT, blue lines) and BAC-TFB1M transgenic (C7.1, red lines) mice are shown. The hearing sensitivity of control and transgenic mice was assessed by measuring ABR after different auditory stimuli. Stimulus intensity thresholds were measured at different frequencies. The medians and quartiles are shown. Male (A) and female (B) mice were analyzed at 4, 7, and 9 months of age. Error bars represent ±SD.
Mentions: We attempted to confirm the report that the Tg-mtTFB1 mice have higher auditory brainstem response (ABR) thresholds across the entire range of frequencies at 3–6 months of age (30). We investigated hearing in BAC-TFB1M (C7.1) mice, after establishing that they overexpress TFB1M to the same extent as Tg-mtTFB1 mice (Fig. 4C and D). Male (Fig. 5A) and female (Fig. 5B) BAC-TFB1M and wild-type mice aged 4 months showed very similar ABRs. However, a subtle, but statistically significant, elevation in ABR thresholds for click ABR and at 24 kHz was seen in female mice of this age (Fig. 5B). ABR measurements were therefore carried out on slightly older mice at 7 and 9 months and revealed no additional difference between BAC-TFB1M and wild-type mice of either sex (Fig. 5A and B). An increase in hearing thresholds at higher frequencies was to be expected, together with a general age-related decline in hearing but, importantly, the TFB1M genotype had no influence on this phenomenon.Figure 5.

Bottom Line: Non-syndromic deafness and predisposition to aminoglycoside-induced deafness can be caused by specific mutations in the 12S rRNA gene of mtDNA and are thus maternally inherited traits.In contrast, it was recently reported that signaling induced by 'hypermethylation' of two conserved adenosines of 12S rRNA in the mitoribosome is of key pathophysiological importance in sensorineural deafness.We thus conclude that therapies directed against mitoribosomal methylation are unlikely to be beneficial to patients with sensorineural hearing loss or other types of mitochondrial disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden.

No MeSH data available.


Related in: MedlinePlus