Artikel ; Online: Loss of the Vitamin B-12 Transport Protein Tcn2 Results in Maternally Inherited Growth and Developmental Defects in Zebrafish.
2021 Band 151, Heft 9, Seite(n) 2522–2532
Abstract: Background: In humans, vitamin B-12 (cobalamin) transport involves 3 paralogous proteins: transcobalamin, haptocorrin, and intrinsic factor. Zebrafish (Danio rerio) express 3 genes that encode proteins homologous to known B-12 carrier proteins: tcn2 (a ... ...
Abstract | Background: In humans, vitamin B-12 (cobalamin) transport involves 3 paralogous proteins: transcobalamin, haptocorrin, and intrinsic factor. Zebrafish (Danio rerio) express 3 genes that encode proteins homologous to known B-12 carrier proteins: tcn2 (a transcobalamin ortholog) and 2 atypical β-domain-only homologs, tcnba and tcnbb. Objectives: Given the orthologous relation between zebrafish Tcn2 and human transcobalamin, we hypothesized that zebrafish carrying null mutations of tcn2 would exhibit phenotypes consistent with vitamin B-12 deficiency. Methods: First-generation and second-generation tcn2-/- zebrafish were characterized using phenotypic assessments, metabolic analyses, viability studies, and transcriptomics. Results: Homozygous tcn2-/- fish produced from a heterozygous cross are viable and fertile but exhibit reduced growth, which persists into adulthood. When first-generation female tcn2-/- fish are bred, their offspring exhibit gross developmental and metabolic defects. These phenotypes are observed in all offspring from a tcn2-/- female regardless of the genotype of the male mating partner, suggesting a maternal effect, and can be rescued with vitamin B-12 supplementation. Transcriptome analyses indicate that offspring from a tcn2-/- female exhibit expression profiles distinct from those of offspring from a tcn2+/+ female, which demonstrate dysregulation of visual perception, fatty acid metabolism, and neurotransmitter signaling pathways. Conclusions: Our findings suggest that the deposition of vitamin B-12 in the yolk by tcn2-/- females may be insufficient to support the early development of their offspring. These data present a compelling model to study the effects of vitamin B-12 deficiency on early development, with a particular emphasis on transgenerational effects and gene-environment interactions. |
---|---|
Mesh-Begriff(e) | Adult ; Animals ; Female ; Humans ; Male ; Maternal Inheritance ; Transcobalamins/genetics ; Vitamin B 12 ; Vitamins ; Zebrafish/genetics |
Chemische Substanzen | Transcobalamins ; Vitamins ; Vitamin B 12 (P6YC3EG204) |
Sprache | Englisch |
Erscheinungsdatum | 2021-06-18 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article ; Research Support, N.I.H., Intramural |
ZDB-ID | 218373-0 |
ISSN | 1541-6100 ; 0022-3166 |
ISSN (online) | 1541-6100 |
ISSN | 0022-3166 |
DOI | 10.1093/jn/nxab151 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
Zusatzmaterialien
Kategorien
Verfügbar in ZB MED Köln/Königswinter
Uc I Zs.205: Hefte anzeigen | Standort: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.