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Comparison of natural and artificial vasopressin deficiency: Why is the latter lethal?

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Russian Journal of Genetics: Applied Research

Abstract

The transgenic mouse technology is widespread in the analysis of physiological functions; however, until now 22.0% of the tested null mutations were found to be lethal. The complete lack of vasopressin (AVP) also resulted in preweaning lethality. It is surprising to take into consideration the viability of the AVP natural mutant Brattleboro rats. Thus, AVP is crucial for survival, but it remains unclear which of its different roles is the most important. AVP exerts its effect through specific plasma membrane receptors. The V1a receptors can induce vasoconstriction maintaining blood pressure during hypovolaemia. The V1b receptor on the anterior pituitary has a role in stress adaptation. The V2 subtype is located in the kidney and contributes to the antidiuresis. The avp gene consists of a signal peptide, AVP, neurophysin 2 and a C-terminal glycopeptide. The naturally occurring AVP-deficient Brattleboro rat has a framshift mutation in the neurophysin portion resulting in central insipidus diabetes. In its hypothalamus AVP is not produced, while in certain peripheral tissues, it may be expressed, suggesting the existence of a different synthetic pathway. The avp knockout mice can also be produced; they will be born, but without the peripheral AVP administration, they will not survive. Comparing the available knockout models, we can conclude that the combined V1a and V2 receptormediated effects, namely, hypotension and water loss, may together led to lethality. As in the Brattleboro and targeted knockout mice the local synthesis of AVP in the heart can be maintained and AVP can be released into the general circulation. Thus, in these animals vasoconstriction can compensate the hypovolemia.

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  1. Institute of Experimental Medicine, Budapest, Hungary

    D. Zelena

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Original Russian Text © D. Zelena, 2016, published in Vavilovskii Zhurnal Genetiki i Selektsii, 2016, Vol. 20, No. 2, pp. 228–233.

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Zelena, D. Comparison of natural and artificial vasopressin deficiency: Why is the latter lethal?. Russ J Genet Appl Res 7, 243–248 (2017). https://doi.org/10.1134/S2079059717030157

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