PMID- 33054837
OWN - NLM
STAT- MEDLINE
DCOM- 20210812
LR  - 20210812
IS  - 1476-511X (Electronic)
IS  - 1476-511X (Linking)
VI  - 19
IP  - 1
DP  - 2020 Oct 14
TI  - Hyperhomocysteinemia and dyslipidemia in point mutation G307S of cystathionine 
      beta-synthase-deficient rabbit generated using CRISPR/Cas9.
PG  - 224
LID - 10.1186/s12944-020-01394-5 [doi]
LID - 224
AB  - BACKGROUND: Congenital hyper-homocysteinemia (HHcy) is caused by a defective 
      cystathionine beta-synthase (CBS) gene, and is frequently associated with 
      dyslipdemia. The aim of this study was to further elucidate the effect of mutated 
      CBS gene on circulating lipids using a rabbit model harboring a homozygous G307S 
      point mutation in CBS. METHODS: CRISPR/Cas9 system was used to edit the CBS gene 
      in rabbit embryos. The founder rabbits were sequenced, and their plasma 
      homocysteine (Hcy) and lipid profile were analyzed. RESULTS: Six CBS-knockout 
      (CBS-KO) founder lines with biallelic modifications were obtained. Mutation in 
      CBS caused significant growth retardation and high mortality rates within 6 weeks 
      after birth. In addition, the 6-week old CBS-KO rabbits showed higher plasma 
      levels of Hcy, triglycerides (TG), total cholesterol (TC) and low-density 
      lipoprotein cholesterol (LDL-C) compared to the age-matched wild-type (WT) 
      controls. Histological analysis of the mutants showed accumulation of 
      micro-vesicular cytoplasmic lipid droplets in the hepatocytes. However, gastric 
      infusion of vitamin B and betaine complex significantly decreased the plasma 
      levels of TG, TC and LDL-C in the CBS-KO rabbits, and alleviated hepatic 
      steatosis compared to the untreated animals. CONCLUSION: A CBS(G307S) rabbit 
      model was generated that exhibited severe dyslipidemia when fed on a normal diet, 
      indicating that G307S mutation in the CBS gene is a causative factor for 
      dyslipidemia.
FAU - Zhang, Ting
AU  - Zhang T
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, 
      China.
AD  - Jiangsu Co-innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China.
FAU - Lu, Rui
AU  - Lu R
AD  - School of Pharmacy, Jiangsu Food & Pharmaceutical Science College, Huaian, 
      223003, Jiangsu, China.
FAU - Chen, Yibing
AU  - Chen Y
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, 
      China.
AD  - Jiangsu Co-innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China.
FAU - Yuan, Yuguo
AU  - Yuan Y
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, 
      China.
AD  - Jiangsu Co-innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China.
FAU - Song, Shaozheng
AU  - Song S
AD  - School of Nursing, Taihu University of Wuxi, Wuxi, 214000, Jiangsu, China.
FAU - Yan, Kunning
AU  - Yan K
AD  - Institute of Translational Medicine, Medical College, Yangzhou University, 
      Yangzhou, 225001, Jiangsu, China.
FAU - Zha, Yiwen
AU  - Zha Y
AD  - Institute of Translational Medicine, Medical College, Yangzhou University, 
      Yangzhou, 225001, Jiangsu, China.
FAU - Zhuang, Wenwen
AU  - Zhuang W
AD  - Institute of Translational Medicine, Medical College, Yangzhou University, 
      Yangzhou, 225001, Jiangsu, China.
FAU - Cheng, Yong
AU  - Cheng Y
AD  - College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, 
      China. chengyong@yzu.edu.cn.
AD  - Jiangsu Co-innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, China. 
      chengyong@yzu.edu.cn.
FAU - Liang, Jingyan
AU  - Liang J
AD  - Institute of Translational Medicine, Medical College, Yangzhou University, 
      Yangzhou, 225001, Jiangsu, China. jyliang@yzu.edu.cn.
LA  - eng
GR  - No. 2016YFE0126000/National Key Research and Development Program of China/
PT  - Journal Article
DEP - 20201014
PL  - England
TA  - Lipids Health Dis
JT  - Lipids in health and disease
JID - 101147696
RN  - 12001-76-2 (Vitamin B Complex)
RN  - 3SCV180C9W (Betaine)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Animals
MH  - Betaine/pharmacology
MH  - Body Weight/genetics
MH  - *CRISPR-Cas Systems
MH  - Cystathionine beta-Synthase/*genetics
MH  - Disease Models, Animal
MH  - Dyslipidemias/*genetics
MH  - Female
MH  - Gene Knockout Techniques
MH  - Hyperhomocysteinemia/*genetics
MH  - Hyperlipidemias/drug therapy/genetics
MH  - Liver/pathology
MH  - Male
MH  - Point Mutation
MH  - Rabbits
MH  - Vitamin B Complex/pharmacology
PMC - PMC7560309
OTO - NOTNLM
OT  - CRISPR/Cas9
OT  - Cystathionine beta-synthase
OT  - Dyslipidemia
OT  - G307S mutation
OT  - Hyperhomocysteinemia
OT  - Rabbits
COIS- The authors declare no conflicts of interest.
EDAT- 2020/10/16 06:00
MHDA- 2021/08/13 06:00
PMCR- 2020/10/14
CRDT- 2020/10/15 17:10
PHST- 2020/07/30 00:00 [received]
PHST- 2020/09/28 00:00 [accepted]
PHST- 2020/10/15 17:10 [entrez]
PHST- 2020/10/16 06:00 [pubmed]
PHST- 2021/08/13 06:00 [medline]
PHST- 2020/10/14 00:00 [pmc-release]
AID - 10.1186/s12944-020-01394-5 [pii]
AID - 1394 [pii]
AID - 10.1186/s12944-020-01394-5 [doi]
PST - epublish
SO  - Lipids Health Dis. 2020 Oct 14;19(1):224. doi: 10.1186/s12944-020-01394-5.