Sporadic congenital malformations of newborn inbred mice

Kalter, Harold

doi:10.1002/tera.1420010208

Cited by 71 publications

(31 citation statements)

References 18 publications

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“…Ocular malformations, which are naturally but rarely observed in C57/BL6 mice, 32 were more frequently and almost unilaterally observed in apelin-KO mice; their incidence in male apelin-KO mice was approximately 6 times higher than that in male wild-type littermates at 4 weeks of age (supplemental Table II). All opaque eyes of apelin-KO mice contained remnants of hyaloid vessels.…”

Section: Discussionmentioning

confidence: 98%

Retardation of Retinal Vascular Development in Apelin-Deficient Mice

Kasai

Shintani

Kato

et al. 2008

ATVB

120

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Objective-Apelin is an endogenous ligand for the G protein-coupled receptor, APJ, and participates in multiple physiological processes. To identify the roles of endogenous apelin, we investigated the phenotype of apelin-deficient (apelin-KO) mice. Methods and Results-Apelin-KO mice showed impaired retinal vascularization and ocular development, which were analyzed by histology, immunohistochemistry, real-time polymerase chain reaction, and the mouse corneal micropocket assay. Apelin-KO mice showed significantly impaired retinal vascularization in the early postnatal period. Retinal apelin/APJ mRNAs were transiently upregulated during the first 2 postnatal weeks but were undetectable in adults. There were no differences in VEGF or FGF2 mRNA expression, or in the morphology and localization of GFAP-positive astrocytes, in the apelin-KO retinas at P5. The corneal pocket assay showed that angiogenic responses to VEGF and FGF2 were remarkably decreased in apelin-KO mice. The reduced responses to VEGF and FGF2 in apelin-KO mice were partially restored by apelin, but apelin alone did not induce angiogenesis. Conclusions-Our See accompanying article on page 1687Apelin/APJ mRNAs are expressed in multiple tissues, primarily in vascular endothelial cells, where they may contribute to angiogenesis. 8,9 Apelin stimulates the proliferation and migration of RF/6A cells, an endothelial cell line of monkey retina, thereby demonstrating angiogenic-like effects. 9 Similarly, apelin is a potent angiogenic factor required for the normal vascular development of frog embryos. 8 During mouse and frog embryonic development, the APJ receptor is highly expressed in endothelial precursor cells and in nascent vascular structures. Apelin is a potent angiogenic factor in 2 in vivo angiogenesis assays, the frog embryo and the chicken chorioallantoic membrane (CAM) assay. 8 More recently, Kidoya et al showed that the apelin/APJ system is involved in the regulation of blood vessel diameter during angiogenesis. 10 In the mouse, the formation of retinal vessels begins at birth and follows a centrifugal extension of retinal vessels from the optic disc to the periphery of the retina. Interestingly, retinal expression of APJ mRNA is observed during the formation of retinal vessels and traces the centrifugal extension of the superficial vasculature bed, whereas that of apelin mRNA is localized in "tip cells," an endothelial subpopulation that forms cell protrusions and directs the polarized extension of the vascular network. 11 In a mouse model of hypoxia-induced retinopathy of prematurity, APJ mRNA transcripts are localized in endothelial cells, and their expression traces the centripetal extension of the retinal network from the periphery of the retina to the optic disc. 12 These findings suggest that apelin/APJ signaling is involved in regulating retinal vascularization.Ocular developmental vascularization is a complex process, which requires the strict coordination of numerous molecular and cellular interactions. Retinal vascularization is contro...

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Section: Discussionmentioning

confidence: 98%

Retardation of Retinal Vascular Development in Apelin-Deficient Mice

Kasai

Shintani

Kato

et al. 2008

ATVB

120

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“…C57Bl/6 mice, from which our transgenic mice were partially derived, have a spontaneous occurrence of microphthalmia, a mutation that particularly affects this strain of mice (Kalter, 1968;Cook and Sulik, 1986). Consistently, mice with microphthalmia were observed among both transgenic derivatives and nontransgenic littermates of the MBP-PDGF-B founder mice.…”

Section: Abnormalities Of Retina Of Mbp-pdgf-b Transgenic Micementioning

confidence: 99%

Oligodendrocyte precursor hypercellularity and abnormal retina development in mice overexpressing PDGF‐B in myelinating tracts

Forsberg-Nilsson¹,

Erlandsson²,

Zhang³

et al. 2003

Glia

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Platelet-derived growth factor (PDGF) influences the generation of neurons and glia during embryogenesis and in early postnatal life. In an attempt to determine the consequences of an overexpression of PDGF-B during the first weeks of life, we targeted transgenic expression of a human PDGF-B cDNA to myelinating tracts using the promoter region of the myelin basic protein (MBP) gene. Transgenic mRNA and protein were expressed in the brain and the expression profile of the human PDGF-B during early postnatal development closely paralleled that of the endogenous mouse MBP gene. The gross morphological appearance of transgenic brains was normal but at the cellular level several phenotypic alterations could be identified. In white matter tracts such as the corpus callosum and cerebellar medulla, there was a marked hypercellularity. The number of oligodendrocyte precursors was increased and astrocytes were more abundant. In adult mice carrying the MBP-PDGF-B transgene, however, myelination appeared normal and the amount of oligodendrocytes was similar to that of control littermates. In addition to the phenotypic alterations in the brain, investigation of eye structure revealed a striking disorganization of retinal architecture. The retina was folded with cells collected in papillar or follicular-like structures. Retinal whole mount preparations after India ink perfusion revealed capillary disorganization with large-caliber vessels supporting only a few fine branches. Our observations strengthen the notion that PDGF is an important effector molecule in postnatal CNS development. GLIA 41:276 -289, 2003.

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“…However, several phenotypes (e.g. microphtalmia, hydrocephalus, and other gene-based anomalies) suggestive of inbreeding have been reported [6], [7].…”

Section: Introductionmentioning

confidence: 99%

The C57BL/6J Mouse Exhibits Sporadic Congenital Portosystemic Shunts

et al. 2013

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C57BL/6 mice are the most widely used strain of laboratory mice. Using in vivo proton Magnetic Resonance Spectroscopy (1H MRS), we have repeatedly observed an abnormal neurochemical profile in the brains of both wild-type and genetically modified mice derived from the C57BL/6J strain, consisting of a several fold increase in cerebral glutamine and two fold decrease in myo-inositol. This strikingly abnormal neurochemical “phenotype” resembles that observed in chronic liver disease or portosystemic shunting and appeared to be independent of transgene, origin or chow and was not associated with liver failure. As many as 25% of animals displayed the abnormal neurochemical profile, questioning the reliability of this model for neurobiology. We conducted an independent study to determine if this neurochemical profile was associated with portosystemic shunting. Our results showed that 100% of the mice with high brain glutamine displayed portosystemic shunting by concomitant portal angiography while all mice with normal brain glutamine did not. Since portosystemic shunting is known to cause alterations in gene expression in many organs including the brain, we conclude that portosystemic shunting may be the most significant problem associated with C57BL/6J inbreeding both for its effect on the central nervous system and for its systemic repercussions.

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Sporadic congenital malformations of newborn inbred mice

Cited by 71 publications

References 18 publications

Retardation of Retinal Vascular Development in Apelin-Deficient Mice

Retardation of Retinal Vascular Development in Apelin-Deficient Mice

Oligodendrocyte precursor hypercellularity and abnormal retina development in mice overexpressing PDGF‐B in myelinating tracts

The C57BL/6J Mouse Exhibits Sporadic Congenital Portosystemic Shunts

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