TY - JOUR

T1 - Morphophysiological effects of insertional mutagenesis of the contactin 5 (Cntn5) gene in transgenic mice

AU - Smirnov, A. V.

AU - Feofanova, N. A.

AU - Kontsevaya, G. V.

AU - Anisimova, M. V.

AU - Kovrigin, I. I.

AU - Serova, I. A.

AU - Moshkin, M. P.

AU - Gerlinskaya, L. A.

AU - Battulin, N. R.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - The transgenesis technologies are actively used in different fields of biological studies. The most actively used method to obtain transgenic animals by DNA injection in the zygote pronucleus can be accompanied by the violation of the genes’ function instead of integrating the transgenic construction. In this work, the morphophysiological effects of integrating the transgenic construction providing the production of the human granulocyte–macrophage colony-stimulating factor in the milk of the mouse line (GM9) (the insertion of the construction in the intron of the contactin 5 (Cntn5) gene) were described. It was demonstrated that the insertion of the construction did not result in the Cntn5 knockout. However, the gene transcription in the heart and kidneys of transgenic animals changes compared with wild-type animals, and the spectrum of transcripts also changes, indicating a violation in the Cntn5 gene splicing regulation. It is known from the published data that the Cntn5 polymorphisms are associated with an addiction to obesity and a predisposition to arterial hypertension. We studied the main parameters of the fat metabolism and cardiovascular activity in mice homozygous for the transgene insertion in the Cntn5 gene, heterozygous animals, and wild-type animals. The phenotyping carried out demonstrates that homozygous mice have a smaller body weight than wild-type individuals. And the weight difference between genotypes is determined more by significantly lower fat accumulation than by the lag of mutants in the development of the skeleton and muscles constituting the lean mass. Statistically significant differences in the parameters characterizing the intensity of the blood circulation were found in the studied lines. Homozygous mice exceed wild-type individuals by their arterial pressure values, heart rate, and blood flow rate in the tail vessels. It should be noted that heterozygous individuals have intermediate values between mutants and wild-type according to all the measured morphofunctional parameters.

AB - The transgenesis technologies are actively used in different fields of biological studies. The most actively used method to obtain transgenic animals by DNA injection in the zygote pronucleus can be accompanied by the violation of the genes’ function instead of integrating the transgenic construction. In this work, the morphophysiological effects of integrating the transgenic construction providing the production of the human granulocyte–macrophage colony-stimulating factor in the milk of the mouse line (GM9) (the insertion of the construction in the intron of the contactin 5 (Cntn5) gene) were described. It was demonstrated that the insertion of the construction did not result in the Cntn5 knockout. However, the gene transcription in the heart and kidneys of transgenic animals changes compared with wild-type animals, and the spectrum of transcripts also changes, indicating a violation in the Cntn5 gene splicing regulation. It is known from the published data that the Cntn5 polymorphisms are associated with an addiction to obesity and a predisposition to arterial hypertension. We studied the main parameters of the fat metabolism and cardiovascular activity in mice homozygous for the transgene insertion in the Cntn5 gene, heterozygous animals, and wild-type animals. The phenotyping carried out demonstrates that homozygous mice have a smaller body weight than wild-type individuals. And the weight difference between genotypes is determined more by significantly lower fat accumulation than by the lag of mutants in the development of the skeleton and muscles constituting the lean mass. Statistically significant differences in the parameters characterizing the intensity of the blood circulation were found in the studied lines. Homozygous mice exceed wild-type individuals by their arterial pressure values, heart rate, and blood flow rate in the tail vessels. It should be noted that heterozygous individuals have intermediate values between mutants and wild-type according to all the measured morphofunctional parameters.

KW - contactin 5

KW - fat metabolism

KW - insertional mutagenesis

KW - transgenesis

UR - http://www.scopus.com/inward/record.url?scp=85038113500&partnerID=8YFLogxK

U2 - 10.1134/S2079059717050185

DO - 10.1134/S2079059717050185

M3 - Article

AN - SCOPUS:85038113500

VL - 7

SP - 799

EP - 805

JO - Russian Journal of Genetics: Applied Research

JF - Russian Journal of Genetics: Applied Research

SN - 2079-0597

IS - 8

ER -