Generation of LEPR Knockout Rabbits with CRISPR/CAS9 System

被引：0

作者：

Yu. Yu. Silaeva ^{[1
]}

P. D. Safonova ^{[2
]}

D. V. Popov ^{[3
]}

M. A. Filatov ^{[1
]}

Yu. D. Okulova ^{[1
]}

R. A. Shafei ^{[4
]}

O. I. Skobel ^{[3
]}

D. E. Vysotskii ^{[3
]}

Yu. D. Gubarev ^{[5
]}

V. I. Glazko ^{[3
]}

T. T. Glazko ^{[3
]}

P. G. Georgiev ^{[2
]}

G. Yu. Kosovsky ^{[3
]}

M. V. Shepelev ^{[1
]}

机构：

[1] Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow

[2] Institute of Gene Biology, Russian Academy of Sciences, Moscow

[3] Afanas’ev Institute of Fur-bearing Animal Breeding and Rabbit Breeding, Moscow Region, Rodniki

[4] Moscow State University, Moscow

[5] Belgorod State National Research University, Belgorod

来源：

Doklady Biological Sciences | 2024年 / 518卷 / 1期

关键词：

CRISPR/Cas9; genetically modified rabbit; LEPR; leptin;

D O I：

10.1134/S0012496624600234

中图分类号：

学科分类号：

摘要：

Abstract: The LEPR gene encodes a leptin hormone receptor, and its mutations are associated with morbid obesity, dysregulation of lipid metabolism, and fertility defects in humans. Spontaneous Lepr mutations have been described in rodents, and Lepr knockout animals have been generated, in particular, using the CRISPR/Cas9 system. Lipid metabolism in rodents significantly differs from that in humans or rabbits, and rabbits are therefore considered as the most relevant model of morbid obesity and lipid metabolism dysregulation in humans. LEPR knockout rabbits have not been reported so far. In this work a LEPR knockout rabbit was generated by introducing a deletion of the region around LEPR exon 10 using the CRISPR/Cas9 system. The body weight of the knockout rabbit was significantly higher than the average body weight of the wild type rabbits. CRISPR/Cas9-mediated generation of LEPR knockout rabbits will allow the development of a model of morbid obesity and endocrine defects due to leptin receptor mutations in humans. © Pleiades Publishing, Ltd. 2024. ISSN 0012-4966, Doklady Biological Sciences, 2024, Vol. 518, pp. 248–255. Pleiades Publishing, Ltd., 2024. ISSN 0012-4966, Doklady Biological Sciences, 2024. Pleiades Publishing, Ltd., 2024.

引用

页码：248 / 255

页数：7

共 23 条

[1]

Alipkina S.I., Leptin and its receptor in normal and pathological conditions, Usp. Sovrem. Biol, 139, pp. 352-364, (2019)

[2]

Friedman J.M., Leptin and the endocrine control of energy balance, Nat. Metab, 1, pp. 754-764, (2019)

[3]

Schaab M., Kratzsch J., The soluble leptin receptor, Best Pract. Res., Clin. Endocrinol. Metab, 29, pp. 661-670, (2015)

[4]

Berger C., Kloting N., Leptin receptor compound heterozygosity in humans and animal models, Int. J. Mol. Sci, 22, (2021)

[5]

Israel D., Chua S., Leptin receptor modulation of adiposity and fertility, Trends Endocrinol. Metab, 21, pp. 10-16, (2010)

[6]

Iikuni N., Leptin and Inflammation, Curr. Immunol. Rev, 4, pp. 70-79, (2008)

[7]

Pennington K.A., Conditional knockout of leptin receptor in the female reproductive tract reduces fertility due to parturition defects in mice, Biol. Reprod, 107, pp. 546-556, (2022)

[8]

Coleman D.L., Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice, Diabetologia, 14, pp. 141-148, (1978)

[9]

Zhang Y., Positional cloning of the mouse obese gene and its human homologue, Nature, 372, pp. 425-432, (1994)

[10]

Chen H., Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice, Cell, 84, pp. 491-495, (1996)

← 1 2 3 →