1 alpha,25-Dihydroxyvitamin D3[1 alpha,25(OH)2D3], an active form of vitamin D, has roles in many biological phenomena such as calcium homeostasis and bone formation, which are thought to be mediated by the 1 alpha,25(OH)2D3 receptor (VDR), a member of the nuclear hormone receptor superfamily. However, the molecular basis for the actions of 1 alpha,25(OH)2D3 in bone formation, its role during development and VDR genetic polymorphisms for predicting bone mineral density are uncertain. To investigate the functional role of VDR, we generated mice deficient in VDR by gene targeting. We report here that in VDR null mutant mice, no defects in development and growth were observed before weaning, irrespective of reduced expression of vitamin D target genes. After weaning, however, mutants failed to thrive, with appearance of alopoecia, hypocalcaemia and infertility, and bone formation was severely impaired as a typical feature of vitamin D-dependent rickets type II (refs 8, 9). Unlike humans with this disease, most of the null mutant mice died within 15 weeks after birth, and uterine hypoplasia with impaired folliculogenesis was found in female reproductive organs. These defects, such as alopoecia and uterine hypoplasia, were not observed in vitamin D-deficient animals. The findings establish a critical role for VDR in growth, bone formation and female reproduction in the post-weaning stage.

Although rachitic/osteomalacic myopathy caused by impaired vitamin D actions has long been described, the molecular pathogenesis remains elusive. To determine physiological roles of vitamin D actions through vitamin D receptor (VDR) in skeletal muscle development, we examined skeletal muscle in VDR gene deleted (VDR -/-) mice, an animal model of vitamin D-dependent rickets type II, for morphological changes and expression of myoregulatory transcription factors and myosin heavy chain isoforms. We found that each muscle fiber was small and variable in size in hindlimb skeletal muscle from VDR -/- mice, although overall myocyte differentiation occurred normally. These abnormalities were independent of secondary metabolic changes such as hypocalcemia and hypophosphatemia, and were accompanied by aberrantly high and persistent expression of myf5, myogenin, E2A, and early myosin heavy chain isoforms, which are normally down-regulated at earlier stages. Moreover, treatment of VDR-positive myoblastic cells with 1,25(OH)2D3 in vitro caused down-regulation of these factors. These results suggest that VDR plays a physiological role in skeletal muscle development, participating in temporally strict down-regulation of myoregulatory transcription factors. The present study can form a molecular basis of VDR actions on muscle and should help further establish the physiological roles of VDR in muscle development as well as pharmacological effects of vitamin D on muscle functions.

We have searched for near-infrared extragalactic background light ( EBL) in the data from the Near-Infrared Spectrometer ( NIRS) on the Infrared Telescope in Space ( IRTS). After subtracting the contribution of faint stars and the zodiacal component based on modeling, a significant isotropic emission is obtained in the wavelength bands from 1.4 to 4.0 m. The spectrum is stellar-like but shows a spectral jump from the optical EBL. The emission obtained is isotropic over the observed sky, and the in-band flux amounts to $35 nW m À2 sr À1 , which is too bright to be explained by the integrated light from faint galaxies. Analyses of COBE DIRBE data, after removal of starlight, show essentially the same result within the uncertainty in the zodiacal light model, which implies that the isotropic emission observed by IRTS NIRS is of extragalactic origin. Significant fluctuations in sky brightness were also detected that cannot be explained by fluctuations due to faint stars, zodiacal components, and normal galaxies. The excess fluctuation amounts to $1/4 of the excess emission over the integrated light of galaxies and is consistent with fluctuations observed by COBE DIRBE. A two-point correlation analysis shows that IRTS NIRS data have an angular scale of fluctuations of a few degrees. The spectrum and brightness of the observed excess EBL emission could be explained by the redshifted UV radiation from the first generation of massive stars ( Population III stars), which caused the reionization of the universe. Recent Wilkinson Microwave Anisotropy Probe (WMAP) observations of the cosmic microwave background (CMB) polarization have indicated that reionization occurred at z $17 or earlier, while the spectral jump around 1 m in the observed excess EBL suggests that the Population III star formation terminated at z $ 9. The observed fluctuations, however, are considerably larger than the theoretical predictions for the Population III stars.

Extragalactic background light (EBL) anisotropy traces variations in the total production of photons over cosmic history, and may contain faint, extended components missed in galaxy point source surveys. Infrared EBL fluctuations have been attributed to primordial galaxies and black holes at the epoch of reionization (EOR), or alternately, intra-halo light (IHL) from stars tidally stripped from their parent galaxies at low redshift. We report new EBL anisotropy measurements from a specialized sounding rocket experiment at 1.1 and 1.6 micrometers. The observed fluctuations exceed the amplitude from known galaxy populations, are inconsistent with EOR galaxies and black holes, and are largely explained by IHL emission. The measured fluctuations are associated with an EBL intensity that is comparable to the background from known galaxies measured through number counts, and therefore a substantial contribution to the energy contained in photons in the cosmos.At near-infrared wavelengths, where the large zodiacal light foreground complicates absolute photometry measurements, the extragalactic background light (EBL) may be best accessed by anisotropy measurements. On large angular scales, fluctuations are produced by the clustering of galaxies, which is driven by the underlying distribution of dark matter. EBL anisotropy measurements can probe emission from epoch of reionization (EOR) galaxies (1-3) and directcollapse black holes (4) that formed during the EOR before the universe was fully ionized by exploiting the distinctive Lyman cutoff feature in the rest-frame ultraviolet (UV), thus probing the UV luminosity density at high redshifts (5). However, large-scale fluctuations may also arise from the intrahalo light (IHL) created by stars stripped from their parent galaxies during tidal interactions (6) at redshift z < 3. A multi-wavelength fluctuation analysis can distinguish among these scenarios and constrain the EOR star formation rate.A search for such background components must carefully account for fluctuations produced 2 by known galaxy populations. Linear galaxy clustering is an important contribution to fluctuations on scales much larger than galaxies themselves. On fine scales, the variation in the number of galaxies produces predominantly Poissonian fluctuations, with an amplitude that depends on the luminosity distribution. Anisotropy measurements suppress foreground galaxy fluctuations by masking known galaxies from an external catalog.The first detections of infrared fluctuations in excess of the contribution from known galaxies with the Spitzer Space Telescope (7-9) were interpreted as arising from a population of faint first-light galaxies at z > 7. The Hubble Space Telescope was used at shorter wavelengths (10) to carry out a fluctuation study in a small deep field but did not report fluctuations in excess of known galaxy populations. Measurements with the AKARIsatellite (11) show excess fluctuations with a blue spectrum rapidly rising from 4.1μm to 2.4μm. Fluctuation measurements in a large survey fi...