RGD Reference Report - Rats deficient C-type natriuretic peptide suffer from impaired skeletal growth without early death. - Rat Genome Database

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Rats deficient C-type natriuretic peptide suffer from impaired skeletal growth without early death.

Authors: Fujii, Toshihito  Hirota, Keisho  Yasoda, Akihiro  Takizawa, Akiko  Morozumi, Naomi  Nakamura, Ryuichi  Yotsumoto, Takafumi  Kondo, Eri  Yamashita, Yui  Sakane, Yoriko  Kanai, Yugo  Ueda, Yohei  Yamauchi, Ichiro  Yamanaka, Shigeki  Nakao, Kazumasa  Kuwahara, Koichiro  Jindo, Toshimasa  Furuya, Mayumi  Mashimo, Tomoji  Inagaki, Nobuya  Serikawa, Tadao  Nakao, Kazuwa 
Citation: Fujii T, etal., PLoS One. 2018 Mar 22;13(3):e0194812. doi: 10.1371/journal.pone.0194812. eCollection 2018.
RGD ID: 127284867
Pubmed: PMID:29566041   (View Abstract at PubMed)
PMCID: PMC5864047   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0194812   (Journal Full-text)

We have previously investigated the physiological role of C-type natriuretic peptide (CNP) on endochondral bone growth, mainly with mutant mouse models deficient in CNP, and reported that CNP is indispensable for physiological endochondral bone growth in mice. However, the survival rate of CNP knockout (KO) mice fell to as low as about 70% until 10 weeks after birth, and we could not sufficiently analyze the phenotype at the adult stage. Herein, we generated CNP KO rats by using zinc-finger nuclease-mediated genome editing technology. We established two lines of mutant rats completely deficient in CNP (CNP KO rats) that exhibited a phenotype identical to that observed in mice deficient in CNP, namely, a short stature with severely impaired endochondral bone growth. Histological analysis revealed that the width of the growth plate, especially that of the hypertrophic chondrocyte layer, was markedly lower and the proliferation of growth plate chondrocytes tended to be reduced in CNP KO rats. Notably, CNP KO rats did not have malocclusions and survived for over one year after birth. At 33 weeks of age, CNP KO rats persisted significantly shorter than wild-type rats, with closed growth plates of the femur in all samples, which were not observed in wild-type rats. Histologically, CNP deficiency affected only bones among all body tissues studied. Thus, CNP KO rats survive over one year, and exhibit a deficit in endochondral bone growth and growth retardation throughout life.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
F344-Nppcem3KyoRatdecreased body length  IMP compared to wild typeRGD 
F344-Nppcem4KyoRatdecreased body length  IMP compared to wild typeRGD 
NppcRatdecreased body length  IMP compared to wild typeRGD 
Nppcem3KyoRatdecreased body length  IMP compared to wild typeRGD 
Nppcem4KyoRatdecreased body length  IMP compared to wild typeRGD 
F344-Nppcem3KyoRatdecreased body weight  IMP compared to wild typeRGD 
F344-Nppcem4KyoRatdecreased body weight  IMP compared to wild typeRGD 
NppcRatdecreased body weight  IMP compared to wild typeRGD 
Nppcem3KyoRatdecreased body weight  IMP compared to wild typeRGD 
Nppcem4KyoRatdecreased body weight  IMP compared to wild typeRGD 
F344-Nppcem3KyoRatdecreased cranium length  IMP compared to wild typeRGD 
F344-Nppcem4KyoRatdecreased cranium length  IMP compared to wild typeRGD 
NppcRatdecreased cranium length  IMP compared to wild typeRGD 
Nppcem3KyoRatdecreased cranium length  IMP compared to wild typeRGD 
Nppcem4KyoRatdecreased cranium length  IMP compared to wild typeRGD 
F344-Nppcem3KyoRatdecreased heart weight  IMP compared to wild typeRGD 
NppcRatdecreased heart weight  IMP compared to wild typeRGD 
Nppcem3KyoRatdecreased heart weight  IMP compared to wild typeRGD 
F344-Nppcem3KyoRatdecreased kidney weight  IMP compared to wild typeRGD 
NppcRatdecreased kidney weight  IMP compared to wild typeRGD 
Nppcem3KyoRatdecreased kidney weight  IMP compared to wild typeRGD 
F344-Nppcem3KyoRatdecreased width of hypertrophic chondrocyte zone  IMP compared to wild typeRGD 
F344-Nppcem4KyoRatdecreased width of hypertrophic chondrocyte zone  IMP compared to wild typeRGD 
NppcRatdecreased width of hypertrophic chondrocyte zone  IMP compared to wild typeRGD 
Nppcem3KyoRatdecreased width of hypertrophic chondrocyte zone  IMP compared to wild typeRGD 
Nppcem4KyoRatdecreased width of hypertrophic chondrocyte zone  IMP compared to wild typeRGD 
F344-Nppcem3KyoRatshort femur  IMP compared to wild typeRGD 
F344-Nppcem4KyoRatshort femur  IMP compared to wild typeRGD 
NppcRatshort femur  IMP compared to wild typeRGD 
Nppcem3KyoRatshort femur  IMP compared to wild typeRGD 
Nppcem4KyoRatshort femur  IMP compared to wild typeRGD 
F344-Nppcem3KyoRatshort radius  IMP compared to wild typeRGD 
F344-Nppcem4KyoRatshort radius  IMP compared to wild typeRGD 
NppcRatshort radius  IMP compared to wild typeRGD 
Nppcem3KyoRatshort radius  IMP compared to wild typeRGD 
Nppcem4KyoRatshort radius  IMP compared to wild typeRGD 
F344-Nppcem3KyoRatshort tibia  IMP compared to wild typeRGD 
F344-Nppcem4KyoRatshort tibia  IMP compared to wild typeRGD 
NppcRatshort tibia  IMP compared to wild typeRGD 
Nppcem3KyoRatshort tibia  IMP compared to wild typeRGD 
Nppcem4KyoRatshort tibia  IMP compared to wild typeRGD 
F344-Nppcem3KyoRatsmall sacral vertebrae  IMP compared to wild typeRGD 
F344-Nppcem4KyoRatsmall sacral vertebrae  IMP compared to wild typeRGD 
NppcRatsmall sacral vertebrae  IMP compared to wild typeRGD 
Nppcem3KyoRatsmall sacral vertebrae  IMP compared to wild typeRGD 
Nppcem4KyoRatsmall sacral vertebrae  IMP compared to wild typeRGD 
Objects Annotated

Genes (Rattus norvegicus)
Nppc  (natriuretic peptide C)
Nppcem3Kyo  (natriuretic peptide C; ZFN induced mutant 3, Kyo)
Nppcem4Kyo  (natriuretic peptide C; ZFN induced mutant 4, Kyo)

Strains
F344-Nppcem3Kyo  (NA)
F344-Nppcem4Kyo  (NA)

Objects referenced in this article
Strain F344-Nppcem1Kyo null Rattus norvegicus
Strain F344-Nppcem2Kyo null Rattus norvegicus

Additional Information