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Knockout of the folate transporter folt-1 causes germline and somatic defects in C. elegans.

Austin MU, Liau WS, Balamurugan K, Ashokkumar B, Said HM, LaMunyon CW - BMC Dev. Biol. (2010)

Bottom Line: Our results show that folt-1(ok1460) knockout hermaphrodites have a substantially reduced germline, generate a small number of functional sperm, and only rarely produce a functional oocyte.We found no evidence of increased apoptosis in the germline of folt-1 knockout mutants, suggesting that germline proliferation is defective.Germline defects associated with folate deficiency appear widespread in animals, being found in humans, mice, fruit flies, and here, nematodes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, California State University Pomona, CA 91768, USA.

ABSTRACT

Background: The C. elegans gene folt-1 is an ortholog of the human reduced folate carrier gene. The FOLT-1 protein has been shown to transport folate and to be involved in uptake of exogenous folate by worms. A knockout mutation of the gene, folt-1(ok1460), was shown to cause sterility, and here we investigate the source of the sterility and the effect of the folt-1 knockout on somatic function.

Results: Our results show that folt-1(ok1460) knockout hermaphrodites have a substantially reduced germline, generate a small number of functional sperm, and only rarely produce a functional oocyte. We found no evidence of increased apoptosis in the germline of folt-1 knockout mutants, suggesting that germline proliferation is defective. While folt-1 knockout males are fertile, their rate of spermatogenesis was severely diminished, and the males were very poor maters. The mating defect is likely due to compromised metabolism and/or other somatic functions, as folt-1 knockout hermaphrodites displayed a shortened lifespan and elongated defecation intervals.

Conclusions: The FOLT-1 protein function affects both the soma and the germline. folt-1(ok1460) hermaphrodites suffer severely diminished lifespan and germline defects that result in sterility. Germline defects associated with folate deficiency appear widespread in animals, being found in humans, mice, fruit flies, and here, nematodes.

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The survivorship of folt-1 knockout mutant worms compared to that of N2 worms.
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Figure 9: The survivorship of folt-1 knockout mutant worms compared to that of N2 worms.

Mentions: Because folt-1 worms lay very few eggs and have reduced production of germ nuclei, we wondered if they might be compromised metabolically. We first measured the rate of defecation, which is sensitive to variations in energy metabolism [33]. folt-1 knockout worms defecated at a significantly reduced rate compared to folt-1/+ heterozygotes and to wild type (F2,33 = 44.48, P < 0.001; Fig. 8). Because defecation rates suggested that folt-1 knockout mutants experienced reduced metabolism, we wondered if they might have extended lifespans [34,35]. Our lifespan results ran counter to the hypothesis: folt-1 knockout worms had significantly shorter life spans of 9.4 ± 0.4 (SEM) days compared to N2 worms which lived 16.9 ± 0.7 days (t = 9.07; P < 0.001; Fig. 9). The decrease in average life span due to the folt-1 knockout was 45%. Therefore, in addition to its effects on the germline, our lifespan and defecation results indicate that the folt-1 gene plays a role in the soma.


Knockout of the folate transporter folt-1 causes germline and somatic defects in C. elegans.

Austin MU, Liau WS, Balamurugan K, Ashokkumar B, Said HM, LaMunyon CW - BMC Dev. Biol. (2010)

The survivorship of folt-1 knockout mutant worms compared to that of N2 worms.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874772&req=5

Figure 9: The survivorship of folt-1 knockout mutant worms compared to that of N2 worms.
Mentions: Because folt-1 worms lay very few eggs and have reduced production of germ nuclei, we wondered if they might be compromised metabolically. We first measured the rate of defecation, which is sensitive to variations in energy metabolism [33]. folt-1 knockout worms defecated at a significantly reduced rate compared to folt-1/+ heterozygotes and to wild type (F2,33 = 44.48, P < 0.001; Fig. 8). Because defecation rates suggested that folt-1 knockout mutants experienced reduced metabolism, we wondered if they might have extended lifespans [34,35]. Our lifespan results ran counter to the hypothesis: folt-1 knockout worms had significantly shorter life spans of 9.4 ± 0.4 (SEM) days compared to N2 worms which lived 16.9 ± 0.7 days (t = 9.07; P < 0.001; Fig. 9). The decrease in average life span due to the folt-1 knockout was 45%. Therefore, in addition to its effects on the germline, our lifespan and defecation results indicate that the folt-1 gene plays a role in the soma.

Bottom Line: Our results show that folt-1(ok1460) knockout hermaphrodites have a substantially reduced germline, generate a small number of functional sperm, and only rarely produce a functional oocyte.We found no evidence of increased apoptosis in the germline of folt-1 knockout mutants, suggesting that germline proliferation is defective.Germline defects associated with folate deficiency appear widespread in animals, being found in humans, mice, fruit flies, and here, nematodes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, California State University Pomona, CA 91768, USA.

ABSTRACT

Background: The C. elegans gene folt-1 is an ortholog of the human reduced folate carrier gene. The FOLT-1 protein has been shown to transport folate and to be involved in uptake of exogenous folate by worms. A knockout mutation of the gene, folt-1(ok1460), was shown to cause sterility, and here we investigate the source of the sterility and the effect of the folt-1 knockout on somatic function.

Results: Our results show that folt-1(ok1460) knockout hermaphrodites have a substantially reduced germline, generate a small number of functional sperm, and only rarely produce a functional oocyte. We found no evidence of increased apoptosis in the germline of folt-1 knockout mutants, suggesting that germline proliferation is defective. While folt-1 knockout males are fertile, their rate of spermatogenesis was severely diminished, and the males were very poor maters. The mating defect is likely due to compromised metabolism and/or other somatic functions, as folt-1 knockout hermaphrodites displayed a shortened lifespan and elongated defecation intervals.

Conclusions: The FOLT-1 protein function affects both the soma and the germline. folt-1(ok1460) hermaphrodites suffer severely diminished lifespan and germline defects that result in sterility. Germline defects associated with folate deficiency appear widespread in animals, being found in humans, mice, fruit flies, and here, nematodes.

Show MeSH
Related in: MedlinePlus