PMID- 28534229
OWN - NLM
STAT- MEDLINE
DCOM- 20180417
LR  - 20181113
IS  - 1573-9368 (Electronic)
IS  - 0962-8819 (Print)
IS  - 0962-8819 (Linking)
VI  - 26
IP  - 4
DP  - 2017 Aug
TI  - Production of a gonadotropin-releasing hormone 2 receptor knockdown (GNRHR2 KD) 
      swine line.
PG  - 567-575
LID - 10.1007/s11248-017-0023-4 [doi]
AB  - Swine are the only livestock species that produce both the second mammalian 
      isoform of gonadotropin-releasing hormone (GNRH2) and its receptor (GNRHR2). 
      Previously, we reported that GNRH2 and GNRHR2 mediate LH-independent testosterone 
      secretion from porcine testes. To further explore this ligand-receptor complex, a 
      pig model with reduced GNRHR2 expression was developed. Small hairpin RNA 
      sequences targeting porcine GNRHR2 were subcloned into a lentiviral-based vector, 
      lentiviral particles were generated and microinjected into the perivitelline 
      space of zygotes, and embryos were transferred into a recipient. One GNRHR2 
      knockdown (KD) female was born that subsequently produced 80 piglets from 6 
      litters with 46 hemizygous progeny (57% transgenic). Hemizygous GNRHR2 KD 
      (n = 10) and littermate control (n = 7) males were monitored at 40, 100, 150, 
      190, 225 and 300 days of age; body weight and testis size were measured and serum 
      was isolated and assayed for testosterone and luteinizing hormone (LH) 
      concentrations. Body weight of GNRHR2 KD boars was not different from littermate 
      controls (P = 0.14), but testes were smaller (P < 0.05; 331.8 vs. 374.8 cm(3), 
      respectively). Testosterone concentrations tended (P = 0.06) to be reduced in 
      GNRHR2 KD (1.6 ng/ml) compared to littermate control (4.2 ng/ml) males, but LH 
      levels were similar (P = 0.47). The abundance of GNRHR2 mRNA was reduced 
      (P < 0.001) by 69% in testicular tissue from mature GNRHR2 KD (n = 5) versus 
      littermate control (n = 4) animals. These swine represent the first 
      genetically-engineered model to elucidate the function of GNRH2 and its receptor 
      in mammals.
FAU - Desaulniers, A T
AU  - Desaulniers AT
AD  - Department of Animal Science, University of Nebraska-Lincoln, A224j Animal 
      Science Building, 3940 Fair Street, Lincoln, NE, 68583-0908, USA.
FAU - Cederberg, R A
AU  - Cederberg RA
AD  - Department of Animal Science, University of Nebraska-Lincoln, A224j Animal 
      Science Building, 3940 Fair Street, Lincoln, NE, 68583-0908, USA.
FAU - Mills, G A
AU  - Mills GA
AD  - Department of Animal Science, University of Nebraska-Lincoln, A224j Animal 
      Science Building, 3940 Fair Street, Lincoln, NE, 68583-0908, USA.
FAU - Lents, C A
AU  - Lents CA
AD  - USDA, Agricultural Research Service, U.S. Meat Animal Research Center, Clay 
      Center, NE, 68933-0166, USA.
FAU - White, B R
AU  - White BR
AD  - Department of Animal Science, University of Nebraska-Lincoln, A224j Animal 
      Science Building, 3940 Fair Street, Lincoln, NE, 68583-0908, USA. 
      bwhite2@unl.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20170522
PL  - Netherlands
TA  - Transgenic Res
JT  - Transgenic research
JID - 9209120
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, LHRH)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 3XMK78S47O (Testosterone)
RN  - 9002-67-9 (Luteinizing Hormone)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified/*genetics/growth & development
MH  - Female
MH  - Gene Expression Regulation
MH  - Gene Knockdown Techniques
MH  - Gonadotropin-Releasing Hormone/biosynthesis/*genetics
MH  - Hemizygote
MH  - Luteinizing Hormone/blood
MH  - Male
MH  - RNA, Small Interfering/genetics
MH  - Receptors, LHRH/biosynthesis/*genetics
MH  - Swine/genetics/growth & development
MH  - Testis/growth & development/metabolism
MH  - Testosterone/blood
PMC - PMC5504211
OTO - NOTNLM
OT  - GNRH2
OT  - GNRHR2
OT  - Gene knockdown
OT  - Porcine
OT  - Testis
OT  - Testosterone
OT  - Transgenic
OT  - shRNA
COIS- CONFLICT OF INTEREST: The authors declare that they have no conflict of interest. 
      HUMAN AND ANIMAL RIGHTS STATEMENT: All animal procedures were approved by the 
      University of Nebraska-Lincoln (UNL) Institutional Animal Care and Use Committee 
      (IACUC). This article does not contain any studies with human participants.
EDAT- 2017/05/24 06:00
MHDA- 2018/04/18 06:00
PMCR- 2017/05/22
CRDT- 2017/05/24 06:00
PHST- 2016/08/30 00:00 [received]
PHST- 2017/05/11 00:00 [accepted]
PHST- 2017/05/24 06:00 [pubmed]
PHST- 2018/04/18 06:00 [medline]
PHST- 2017/05/24 06:00 [entrez]
PHST- 2017/05/22 00:00 [pmc-release]
AID - 10.1007/s11248-017-0023-4 [pii]
AID - 23 [pii]
AID - 10.1007/s11248-017-0023-4 [doi]
PST - ppublish
SO  - Transgenic Res. 2017 Aug;26(4):567-575. doi: 10.1007/s11248-017-0023-4. Epub 2017 
      May 22.