Behavioural and reproductive characteristics of heterozygous TPH2 knockout mice

DOI: 10.29296/2618723X-2021-03-01

A.A. Kibitkina, ORCID 0000-0001-6934-7342;  
E.V. Vasilevskaya, ORCID 0000-0002-4752-3939;
G.S. Tolmacheva, ORCID0000-0001-9937-320X;
L.V. Fedulova, ORCID0000-0003-3573-930X

V.M. Gorbatov Federal Research Center for Food Systems, Russian Academy of Sciences,
109316, Russia, Moscow, Talalikhina Street, 26
Е-mail: [email protected]

Keywords: TPH2 gene estrous cycle sexual preferences aggression

For citation:

Kibitkina A.A., Vasilevskaya E.V., Tolmacheva G.S., Fedulova L.V. Behavioural and reproductive characteristics of heterozygous TPH2 knockout mice. Laboratory Animals for Science. 2021; 3.


TPH2 mutant mice are a highly accurate model for several mental illnesses such as autism, attention deficit disorder, and obsessive-compulsive and depressive disorders. The gene encoding a protein tryptophan hydroxylase-2 (TPH2) is one of the key ones in serotonergic neuromediation, providing the rate and synthesis of serotonin from tryptophan. Impulsivity, aggression, as well as impaired memory, cognition, and information processing characterize the phenotypic profile of homozygous TPH2 knockout mice. In the process of maintaining a colony of knockout mice by harem, mating of heterozygous individuals, episodic attacks of female aggression, reduced reproductive activity, and lack of normal sexual behavior towards males can occur. However, such questions with regard to heterozygous TPH2 knockout mice remain poorly understood. To determine the factors potentially affecting the success of breeding TPH2 mice, the estrous cycle of heterozygous females was experimentally studied by visual assessment and cytology, the sex preferences of sexually naive and experienced female and male mice in the binary test with a urinary tag, social interactions between same-sex conspecifics in the dyadic test "resident intruder". Disturbances in the estrous cycle of heterozygous TPH2 females were revealed, in particular, a longer stage of diestrus, and, as a consequence, a reduction in the number of cycles. The influence of the gene factor is not involved in determining sexual preferences based on olfactory information. However, male and female TPH2 Het (both naive and experienced) showed significantly greater interest in naive individuals TPH2 Het and Wt. TPH2 Het females did not exhibit aggressive-competing behavior during paired contact with TPH2 Het and Wt females, which indicates the applicability of the harem breeding strategy. Thus, the studied factors should be taken into account when maintaining a colony of TPH2 mutant mice during the preparation of animals for the breeding cycle.

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Author’s Contribution

Vasilevskaya E.V. – сonceptualization, data analysis, review and editing;
Kibitkina A.A. – methodology, realization, date collection and analysis, writing-original draft preparation;
Tolmacheva G.S. – realization, date collection, editing;
Fedulova L.V. – project administration, review and editing.

Conflict of interest

The authors declare no conflicts of interest.


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