A single nucleotide mutation in Nppc is associated with a long bone abnormality in lbab mice

Jiao, Yan; Yan, Jian; Jiao, Feng; Yang, Hong; Donahue, Leah Rae; Li, Xinmin; Roe, Bruce A.; Stuart, J.; Gu, Weikuan

doi:10.1186/1471-2156-8-16

Cited by 29 publications

(23 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These phenotypes were attributed to abnormal bone development in the absence of CNP-Npr2 signaling, as similar defects were found in mice with targeted deletion of CNP or Npr2 (9,10) and in the spontaneous Npr2 mutant (cn) (11). Furthermore, a missense mutation was recently mapped to the Nppc gene that results Arg to Gly substitution in the receptor binding and hence the loss of CNP activity (12). Because the general embryonic development is not affected in this mutant, the lbab mouse provides a useful loss-of-function model to investigate CNP functions in the developing spinal cord.…”

Section: Loss Of Cnp Leads To Impaired Sensory Axon Bifurcationmentioning

confidence: 71%

See 1 more Smart Citation

Regulation of axonal development by natriuretic peptide hormones

Zhao

Ma²

2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Section: Loss Of Cnp Leads To Impaired Sensory Axon Bifurcationmentioning

confidence: 71%

“…004521), and mutant animals were generated by crossing heterozygous animals with the plug day as E0.5. The genotype was determined by AvaII digestion of the PCR product, amplified from primers 5Ј-CTCTTGGGTGCAGAGCTAGG-3Ј and 5Ј-AGCTGGTGGCAATCAGAAAA-3Ј (12).…”

Section: Size Of Axonal Halos (µM)mentioning

confidence: 99%

Regulation of axonal development by natriuretic peptide hormones

Zhao

Ma²

2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

“…However, the overall role of NPPC/NPR2 signaling in female reproduction, including follicle development, oocyte maturation, and ovulation, remains to be elucidated. Achondroplasia (CN) and long bone abnormality (LBAB) are spontaneous mutant mouse strains characterized by disproportionate dwarfism with short limbs and tails (Lane & Dickie 1968, Jiao et al 2007). Missense mutations have been identified as the causative genetic alterations in the Npr2 and Nppc genes of the CN and LBAB mice respectively (Tsuji & Kunieda 2005, Jiao et al 2007.…”

Section: Introductionmentioning

confidence: 99%

NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation during follicular development in the mouse ovary

Kiyosu¹,

Tsuji²,

Yamada³

et al. 2012

Reproduction

View full text Add to dashboard Cite

Natriuretic peptide type C (NPPC) and its high affinity receptor, natriuretic peptide receptor 2 (NPR2), have been assumed to be involved in female reproduction and have recently been shown to play an essential role in maintaining meiotic arrest of oocytes. However, the overall role of NPPC/NPR2 signaling in female reproduction and ovarian function is still less clear. Here we report the defects observed in oocytes and follicles of mice homozygous for antral follicles prematurely resumed meiosis and that immediately before ovulation, oocytes showed disorganized chromosomes or fragmented ooplasm; and iv) ovulated oocytes and oocytes in the periovulatory follicles of the mutant mice were devoid of cumulus cells. These findings demonstrate that NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation, which affects female fertility through the production of oocytes with developmental capacity.

show abstract

“…Two strains of dwarf mice, one with an autosomal recessive mutant gene, named cn/cn [34], and shortlimbed dwarfism (SLW) mice [35], possess spontaneous loss of function mutations in the GC-B gene. Another strain of dwarf mice, named long bone abnormality (Lbab) mice, displays a loss of function mutation in the CNP gene [37]; the resulting short stature phenotype and impaired endochondral bone growth could be abrogated by targeted overexpression of CNP in the growth plate cartilage [36].…”

Section: I-3 Skeletal Phenotypes Of Spontaneous Mutant Animals Of Thmentioning

confidence: 99%

Translational research of C-type natriuretic peptide (CNP) into skeletal dysplasias

Yasoda

Nakao

2010

Endocr J

View full text Add to dashboard Cite

Abstract. By using transgenic and knockout mice, we have elucidated that C-type natriuretic peptide (CNP) is a potent stimulator of endochondral bone growth. In humans, loss-of-function mutations in the gene coding for guanylyl cyclase-B (GC-B), the specific receptor for CNP, have been proved to be the cause of acromesomelic dysplasia, type Maroteaux, one form of human skeletal dysplasias. Following these results, we have started to translate the stimulatory effect of CNP on endochondral bone growth into the therapy for patients with skeletal dysplasias. We have shown that targeted overexpression of CNP in cartilage or systemic administration of CNP reverses the impaired skeletal growth of mice model of achondroplasia, the most common form of human skeletal dysplasias. Key words: C-type natriuretic peptide (CNP), Guanylyl cyclase-B (GC-B), Skeletal dysplasia, Achondroplasia, Translational researchThe nATriureTic peptide family consists of three structurally related peptides, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) [1]. The biological actions of natriuretic peptides are mediated by activation of two subtypes of membranous guanylyl cyclase (GC), GC-A and GC-B, followed by intracellular accumulation of cyclic GMP (cGMP) [2]. The rank order of potency to induce cGMP production via GC-A is ANP ≥ BNP >> CNP, while that via GC-B is CNP > ANP ≥ BNP [3]. Therefore, ANP and BNP serve as endogenous ligands for GC-A, whereas CNP is specific for GC-B. A third natriuretic peptide receptor with no intracellular guanylyl cyclase domain, dubbed the clearance receptor (C-receptor), is thought to be engaged in the receptor-mediated degradation of natriuretic peptides [2]. The ANP, BNP/GC-A system plays a pivotal role in the regulation of cardiovascular homeostasis, as demonstrated by their augmentation in various pathophysiological states such as heart failure [4][5][6][7][8], myocardial infarction [9, 10], cardiac hypertrophy [11,12], and hypertension [13][14][15]. In fact, ANP and BNP are cardiac hormones secreted primarily by the atrium and ventricle of the heart, respectively [8,15], with strong diuretic, natriuretic, and vasodilatory activities [4, 5, 8]. ANP and BNP are used in the treatment of heart failure [16,17] and serve as sensitive biochemical markers for heart failure and cardiac hypertrophy [6][7][8]. CNP, the third member of natriuretic peptide family, was first purified from porcine brain [18]. While CNP is the primary natriuretic peptide in the human brain [19], it is also produced by vascular endothelial cells [20][21][22] and macrophages [23], and is thought to act as an autocrine/paracrine regulator and as a neuropeptide [19]. Furthermore, analysis of genetically engineered mice of the CNP/GC-B system revealed that CNP and GC-B play a pivotal role in the regulation of endochondral bone growth.i. The growth promoting effect of the cnP/Gc-B system on endochondral bone growth I-1. Skeletal phenotypes of genetically engineered mice of the CNP/GC-B sys...

show abstract

A single nucleotide mutation in Nppc is associated with a long bone abnormality in lbab mice

Cited by 29 publications

References 15 publications

Regulation of axonal development by natriuretic peptide hormones

Regulation of axonal development by natriuretic peptide hormones

NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation during follicular development in the mouse ovary

Translational research of C-type natriuretic peptide (CNP) into skeletal dysplasias

Contact Info

Product

Resources

About