Nnt mutation and function

Nnt mutation

    • Mice with Nnt mutations, such as C57BL6/J (B6J), have a normal, healthy life-span with no overt abnormalities.
    • The Nnt mutation was detected in 2006 when QTL analysis revealed it correlated with robust weight gain and impaired glucose tolerance in B6J mice fed a high fat (60 kcal%) diet in a diet-induced-obesity (DIO) study (Freeman et al. Diabetes 2006). Read more about Nnt in B6J DIO mice.
    • Mutations in Nnt have not been linked to human disease. Given the increased weight gain of B6J in response to a high fat diet, Nnt mutations may be correlated to abnormalities in glucose homeostasis in humans.

Nnt function

The nicotinamide nucleotide transhydrogenase (Nnt) gene encodes a mitochondrial protein that catalyzes production of NADPH which participates in ATP synthesis. The normal lifespan of the B6J suggests that Nnt is not critical for normal cellular function.

The importance of mutations in biomedical research

  • A mouse without mutations is not a model of human disease. A spectrum of mutations gives each strain their unique phenotypic profile. Nnt is one mutation that contributes to the unique genetic profile of the B6J, the most published and widely used mouse model in biomedical research.
  • The B6J and B6NJ are part of a unique genetic stability program (GSP) (Taft et al. 2006) to minimize genetic drift, maintain unique phenotypes, and insure data reproducibility across generations of scientific researchers.

Frequenty asked questions about Nnt.

References

Freeman HC, Hugill A, Dear NT, Ashcroft FM, Cox RD. 2006. Deletion of Nicotinamide Nucleotide Transhydrogenase: A New Quantitative Trait Locus Accounting for Glucose Intolerance in C57BL/6J Mice. Diabetes 55(7):2153-6. [PubMed: 16804088].

Taft RA, Davisson M and Wiles MV. 2006. Know thy mouse. Trends Genet 22(12):649-53. [PubMed: 17007958].