Homologous genes for X-linked chondrodysplasia punctata in man and mouse

Happle, Rudolf; Phillips, Rita J. S.; Roessner, Albert; Jünemann, G

doi:10.1007/bf00285392

Cited by 60 publications

(13 citation statements)

References 8 publications

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“…Lens cortical "frost figure" opacities are present. Bpa is considered as a model for human X-linked syndrome chondrodysplasia punctata (Happle et al, 1983;Angel et al, 1993). The mutation vacuolated lens (vl) is mapped to mouse chromosome 1 and leads to opaque white lenses.…”

Section: Mutants Waiting For Molecular Characterizationmentioning

confidence: 99%

Congenital hereditary cataracts

Graw¹

2004

Int. J. Dev. Biol.

126

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Congenital cataracts are rare and occur in developed countries with a frequency of 30 cases among 100,000 births with a further 10 cases being diagnosed during childhood. They reflect mainly genetically caused developmental alterations in the lens and surrounding ocular tissues. Even if modern Human Genetics has made large steps forward in the characterization of human hereditary disorders, the underlying developmental processes can only be investigated in model organisms. The mouse is such a good model because of its similarity (as a mammal) and its genetic characterization. This review brings together our genetic and developmental knowledge of congenital, human cataracts with the corresponding mouse models. First, early events will be influenced by genes coding for transcription factors like Pax6, Pitx3, Maf or Sox. If the lens is maturing, mutations affecting the lens membranes (aquaporins/Mip, Lim-2 or connexins) or the structural proteins of the cytosol of the lens fiber cells (the crystallins) become more important. From a genetic point of view it becomes obvious that cataract-causing mutations are not distributed randomly. The discovery of a broad variety of genes important for eye and lens development made much progress in the recent years. Nevertheless, there still remains a long list of mutations to be characterized and functionally investigated both in mouse and man indicating a broad genetic heterogeneity in that which clinicians simply refer to as a "cataract".

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Section: Mutants Waiting For Molecular Characterizationmentioning

confidence: 99%

Congenital hereditary cataracts

Graw¹

2004

Int. J. Dev. Biol.

126

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“…The hallmark of affected females is the development hyperkeratotic eruptions in the skin at postnatal day 5 that resolve to hairless patches after 2–3 weeks [14]. They also display skeletal defects, occasional microphthalmia, and, on average, are smaller than wild type (WT) littermates at birth [15]. Mutations in the human NSDHL gene cause CHILD syndrome, a rare disorder causing early embryonic lethality in males, and unilateral skin defects and limb reduction in females [16–18].…”

Section: Introductionmentioning

confidence: 99%

Developmental expression pattern of the cholesterogenic enzyme NSDHL and negative selection of NSDHL-deficient cells in the heterozygous Bpa1H/+ mouse

Cunningham

Spychala

McLarren

et al. 2009

Molecular Genetics and Metabolism

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NSDHL (NAD(P)H sterol dehydrogenase-like), is a 3β-hydroxysterol dehydrogenase thought to function in the demethylation of sterol precursors in one of the later steps of cholesterol biosynthesis. Mutations in the X-linked NSDHL gene cause CHILD syndrome in humans, and the male-lethal bare patches (Bpa) phenotype in mice. The relative level of NSDHL expression among different mouse tissues at several stages of embryogenesis and postnatal development was analyzed by immunohistochemistry. In wild type (WT) embryos, the highest levels of expression were seen in the liver, dorsal root ganglia, central nervous system, retina, adrenal gland and testis. Heterozygous Bpa1H females are mosaic for NSDHL expression due to normal random X inactivation. NSDHL deficient cells were detected in the developing cerebral cortex and retina of Bpa1H female embryos. In postnatal WT and Bpa1H animals, we compared the expression pattern of NSDHL in skin, an affected tissue; liver, a main site of cholesterol synthesis; and brain, a tissue dependent on endogenous synthesis of cholesterol due to lack of transport across the blood-brain barrier. Clonal populations of mutant cells were visible in the brain, skin and liver of Bpa1H pups. In the liver, the proportion of NSDHL negative cells dropped from ~50% at postnatal day 6 to ~20% at one year of age. In the brain, which showed the highest expression in cerebral cortical and hippocampal neurons, the proportion of NSDHL negative cells also dropped dramatically over the first year of life. Our results suggest that while NSDHL deficient cells in the mosaic Bpa1H female are able to survive and differentiate during embryonic development, they are subject to negative selection over the life of the animal.

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“…The skin lesions found in the mouse (linear pigmentary disturbances, linear arrangement of hyperkeratosis, linear absence of hair) correspond to the cutaneous markers of X-linked dominant chondrodysplasia punctata in humans. In 1983, Happle et al [18] demonstrated homology also for the skel etal and ocular abnormalities. The locus for Bpa has re cently been shown to be located between the a,-subunit of the receptor for y-aminobutyric acid (Gaba 3) and the murine X-linked visual pigment gene [19].…”

Section: Discussionmentioning

confidence: 99%

X-Linked Dominant Chondrodysplasia punctata (Happle Syndrome) with Uncommon Symmetrical Shortening of the Tubular Bones

Gobello¹,

Mazzanti²,

Fileccia³

et al. 1995

Dermatology

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We describe the case of a 13-year-old girl suffering from chondrodysplasia punctata, associated with ichthyosis arranged along Blaschko’s lines, follicular atrophoderma, cicatricial alopecia and coarse, lusterless hair. The patient also showed a congenital cataract of the right eye, dysplastic facial appearance and symmetrical shortening of the tubular bones. The pathogenetic concept of functional X-chromosome mosaicism is reviewed as well as the recent results obtained by molecular research that have failed, so far, to solve the problem of regional assignment of the underlying X-linked gene.

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Homologous genes for X-linked chondrodysplasia punctata in man and mouse

Cited by 60 publications

References 8 publications

Congenital hereditary cataracts

Congenital hereditary cataracts

Developmental expression pattern of the cholesterogenic enzyme NSDHL and negative selection of NSDHL-deficient cells in the heterozygous Bpa1H/+ mouse

X-Linked Dominant Chondrodysplasia punctata (Happle Syndrome) with Uncommon Symmetrical Shortening of the Tubular Bones

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