PMID- 30239744
OWN - NLM
STAT- MEDLINE
DCOM- 20190614
LR  - 20190614
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 28
IP  - 1
DP  - 2019 Jan 1
TI  - C-type natriuretic peptide improves growth retardation in a mouse model of 
      cardio-facio-cutaneous syndrome.
PG  - 74-83
LID - 10.1093/hmg/ddy333 [doi]
AB  - Cardio-facio-cutaneous (CFC) syndrome, a genetic disorder caused by germline 
      mutations in BRAF, KRAS, MAP2K1 and MAP2K2, is characterized by growth 
      retardation, heart defects, dysmorphic facial appearance and dermatologic 
      abnormalities. We have previously reported that knock-in mice expressing the CFC 
      syndrome-associated mutation, Braf Q241R, showed growth retardation because of 
      gastrointestinal dysfunction. However, other factors associated with growth 
      retardation, including chondrogenesis and endocrinological profile, have not been 
      examined. Here, we show that 3- and 4-week-old BrafQ241R/+ mice have decreased 
      body weight and length, as well as reduced growth plate width in the proximal 
      tibiae. Furthermore, proliferative and hypertrophic chondrocyte zones of the 
      growth plate were reduced in BrafQ241R/+ mice compared with Braf+/+ mice. 
      Immunohistological analysis revealed that extracellular signal-regulated kinase 
      (ERK) activation was enhanced in hypertrophic chondrocytes in BrafQ241R/+ mice. 
      In accordance with growth retardation and reduced growth plate width, decreased 
      serum levels of insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 
      (IGFBP-3) were observed in BrafQ241R/+ mice at 3 and 4 weeks of age. Treatment 
      with C-type natriuretic peptide (CNP), a stimulator of endochondral bone growth 
      and a potent inhibitor of the FGFR3-RAF1-MEK/ERK signaling, increased body and 
      tail lengths in Braf+/+ and BrafQ241R/+ mice. In conclusion, ERK activation in 
      chondrocytes and low serum IGF-1/IGFBP-3 levels could be associated with the 
      growth retardation observed in BrafQ241R/+ mice. Our data also suggest that CNP 
      is a potential therapeutic target in CFC syndrome.
FAU - Inoue, Shin-Ichi
AU  - Inoue SI
AD  - Department of Medical Genetics, Tohoku University School of Medicine, Sendai.
FAU - Morozumi, Naomi
AU  - Morozumi N
AD  - Immunology and Inflammatory Disease Field, Asubio Pharma Co., Ltd, Kobe.
FAU - Yoshikiyo, Kazunori
AU  - Yoshikiyo K
AD  - Immunology and Inflammatory Disease Field, Asubio Pharma Co., Ltd, Kobe.
FAU - Maeda, Hiroaki
AU  - Maeda H
AD  - Immunology and Inflammatory Disease Field, Asubio Pharma Co., Ltd, Kobe.
AD  - End-Organ Disease Laboratories, Daiichi Sankyo Co., Ltd, Tokyo, Japan.
FAU - Aoki, Yoko
AU  - Aoki Y
AD  - Department of Medical Genetics, Tohoku University School of Medicine, Sendai.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (insulin-like growth factor-1, mouse)
RN  - 127869-51-6 (Natriuretic Peptide, C-Type)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.1.- (MAP2K2 protein, human)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Braf protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
RN  - Cardiofaciocutaneous syndrome
SB  - IM
MH  - Animals
MH  - Chondrocytes/physiology
MH  - Disease Models, Animal
MH  - Ectodermal Dysplasia/*metabolism/physiopathology
MH  - Facies
MH  - Failure to Thrive/*metabolism/physiopathology
MH  - Germ-Line Mutation
MH  - Growth Disorders/metabolism
MH  - Heart Defects, Congenital/*metabolism/physiopathology
MH  - Humans
MH  - Insulin-Like Growth Factor I/analysis
MH  - MAP Kinase Kinase 1/genetics
MH  - MAP Kinase Kinase 2/genetics
MH  - MAP Kinase Signaling System/genetics/physiology
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Mutation
MH  - Natriuretic Peptide, C-Type/metabolism/*pharmacology
MH  - Proto-Oncogene Proteins B-raf/*genetics/physiology
EDAT- 2018/09/22 06:00
MHDA- 2019/06/15 06:00
CRDT- 2018/09/22 06:00
PHST- 2018/06/22 00:00 [received]
PHST- 2018/09/13 00:00 [accepted]
PHST- 2018/09/22 06:00 [pubmed]
PHST- 2019/06/15 06:00 [medline]
PHST- 2018/09/22 06:00 [entrez]
AID - 5099468 [pii]
AID - 10.1093/hmg/ddy333 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2019 Jan 1;28(1):74-83. doi: 10.1093/hmg/ddy333.