Biomedical subjects

George W Smith

Publications and source records attributed to George W Smith.

At least 19 recordsLinked to original sources

PubMed2006

Novel algorithm for transcriptome analysis.

A growing body of evidence implicates the oocyte as a key regulator of ovarian folliculogenesis and early embryonic development. We have screened bovine cDNA microarrays (containing expressed sequence tags representing >15,000 unique genes) with Cy3- and Cy5-labeled cDNA derived from bovine oocyte samples collected at two different stages of meiotic maturation (germinal vesicle vs. metaphase II; n = 3 samples per group). Here, we present a novel data analysis approach that uses all available information from above experiments to obtain and index the transcriptome of bovine oocytes and changes in transcriptome composition in response to meiotic maturation. Signal intensities (Fg) for all housekeeping genes were omitted prior to analysis. A local threshold for gene expression was computed as background intensity (Bg) plus 2 times the standard deviation of background and foreground signals. Within each array, data were normalized by the LOWESS procedure. Subsequently, a two-stage mixed model was fitted to remove systematic variations. In the first stage, the response was the LOWESS normalized Fg with treatment as a fixed effect. In stage 2, the residuals from stage 1 were analyzed in a gene-specific model that included treatment group and spots nested within patch and array. A test for the difference between least squares means for the treatment effect was performed. A false discovery rate (FDR) adjustment on the p values for the difference was carried out. This novel algorithm was compared with approaches that ignore the FDR and the threshold described herein and stark differences obtained.

Algorithms↗

PubMed2006

Decreased ACTH secretion during prolonged transportation stress is associated with reduced pituitary responsiveness to tropic hormone stimulation in cattle.

The present study examined the effect of transportation stress on hypothalamic-pituitary-adrenal axis responsiveness to tropic hormone stimulation and on abundance of corticotropin releasing factor (CRF) receptor R1 (CRFR1) and arginine vasopressin (AVP) receptor V3 (V3) mRNAs in the anterior pituitary (AP) of cattle. Holstein steers were transported for 10 h or used as non-transported controls (NTC). Blood samples were collected at start of transportation and every 1-2h thereafter. To test AP responsiveness to tropic hormones, animals were challenged (i.v.) with CRF (0.5 microg/kg), AVP (1 microg/kg) or CRF plus AVP immediately after end of transportation and blood samples collected every 30 min for 3h. The AP of animals transported for 0, 4 or 10 h were harvested for mRNA analyses. Plasma ACTH in transported animals increased within 1h and remained elevated for 6 and 8h versus NTC and 0 h values, respectively. Plasma concentrations of cortisol increased in response to transportation and remained elevated throughout the transport period. Injection of CRF or AVP to NTC animals increased plasma ACTH, but ACTH secretion in response to CRF or AVP was dramatically reduced in transported animals. ACTH secretion following co-injection of CRF and AVP tended to be less in transported animals, but was almost 100% greater than when secretagogues were administered separately. Despite decreased AP responsiveness to CRF and AVP, AP CRFR1 and V3 mRNAs were increased after 10 h transportation. Results indicate decreased AP responsiveness to CRF and AVP may regulate duration of ACTH secretion in response to transportation stress in cattle.

Adrenocorticotropic Hormone↗

PubMed2006

Evidence of a local negative role for cocaine and amphetamine regulated transcript (CART), inhibins and low molecular weight insulin like growth factor binding proteins in regulation of granulosa cell estradiol production during follicular waves in cattle.

The ability of ovarian follicles to produce large amounts of estradiol is a hallmark of follicle health status. Estradiol producing capacity is lost in ovarian follicles before morphological signs of atresia. A prominent wave like pattern of growth of antral follicles is characteristic of monotocous species such as cattle, horses and humans. While our knowledge of the role of pituitary gonadotropins in support of antral follicle growth and development is well established, the intrinsic factors that suppress estradiol production and may help promote atresia during follicular waves are not well understood. Numerous growth factors and cytokines have been reported to suppress granulosa cell estradiol production in vitro, but the association of expression of many such factors in vivo with follicle health status and their physiological significance are not clear. The purpose of this review is to discuss the in vivo and in vitro evidence supporting a local physiological role for cocaine and amphetamine regulated transcript, inhibins and low molecular weight insulin like growth factor binding proteins in negative regulation of granulosa cell estradiol production, with emphasis on evidence from the bovine model system.

Animals↗

PubMed2006

Quantitative analysis of messenger RNA abundance for ribosomal protein L-15, cyclophilin-A, phosphoglycerokinase, beta-glucuronidase, glyceraldehyde 3-phosphate dehydrogenase, beta-actin, and histone H2A during bovine oocyte maturation and early embryogenesis in vitro.

Real-time reverse transcription PCR has greatly improved the ease and sensitivity of quantitative gene expression studies. However, measurement of gene expression generally requires selection of a valid reference (housekeeping gene) for data normalization to compensate for inherent variations. Given the dynamic nature of early embryonic development, application of this technology to studies of oocyte and early embryonic development is further complicated due to limited amounts of starting material and a paucity of information on constitutively expressed genes for data normalization. We have validated quantitative procedures for real-time reverse transcription polymerase chain reaction (RT-PCR) analysis of mRNA abundance during bovine meiotic maturation and early embryogenesis and utilized this technology to determine temporal changes in mRNA abundance for ribosomal protein L-15, cyclophilin-A, phosphoglycerokinase, beta-glucuronidase, glyceraldehyde-3-phosphate dehydrogenase, beta-actin, and histone H2A. Quantification of amounts of specific exogenous RNAs added to samples revealed acceptable rates of RNA recovery and efficiency of reverse transcription with minimal variation. Progression of bovine oocytes to metaphase II resulted in reduced abundance of polyadenylated, but not total transcripts for majority of above genes; however phosphoglycerokinase exhibited a significant decline in both RNA populations. Abundance of mRNAs for above genes in early embryos generally remained low until the blastocyst stage, but abundance of ribosomal protein L-15 mRNA was increased at the morula stage and histone H2A mRNA showed dynamic changes prior to embryonic genome activation. Results demonstrate a valid approach for quantitative analysis of mRNA abundance in oocytes and embryos, but do not support constitutive expression of above genes during early embryonic development.

Actins↗

PubMed2006

Effect of intrafollicular indomethacin injection on gonadotropin surge-induced expression of select extracellular matrix degrading enzymes and their inhibitors in bovine preovulatory follicles.

A growing body of evidence supports an obligatory role for intrafollicular prostanoids in the mechanism of ovulation. However, the prostanoid-dependent mediators of the follicular extracellular matrix degradation required for ovulation are unknown. The objectives of this study were to determine the cellular compartment(s) in which the gonadotropin surge-induced regulation of select extracellular matrix degrading enzymes and their cognate inhibitors occurs in bovine preovulatory follicles, and to test whether such regulation is blocked by intrafollicular administration of the prostanoid synthesis and ovulation inhibitor, indomethacin (INDO). Follicular fluid prostaglandin E2 concentrations were elevated in diluent-treated follicles before ovulation (24 h after GnRH injection), but the increase was blocked in INDO-treated follicles. Real-time PCR analysis revealed the specific follicular cell types where gonadotropin surge-induced increases in mRNA abundance for members of the matrix metalloproteinase/tissue inhibitor of metalloproteinase and plasminogen activator families occurred. INDO treatment increased thecal cell mRNA for tissue inhibitor of metalloproteinase-4 and its protein abundance in the apex of preovulatory follicles before ovulation, but suppressed granulosal cell mRNA and activity for tissue plasminogen activator in follicular fluid and the follicle apex. Plasmin activity was also suppressed in the follicular fluid of INDO-treated follicles. Effects of INDO injection on select matrix metalloproteinases were not observed. The results suggest that gonadotropin surge-induced regulation of tissue inhibitor of metalloproteinase-4 and tissue plasminogen activator may be prostanoid dependent, and support a potential role for increased tissue plasminogen activator expression and decreased tissue inhibitor of metalloproteinase-4 expression in the mechanism of ovulation.

Animals↗

PubMed2005

Validation and application of a high fidelity mRNA linear amplification procedure for profiling gene expression.

The need for microgram quantities of RNA for microarray experiments has hindered application of this novel technology in cell types/tissue samples with limited abundance of RNA. In this study, potential application of T7-based linear RNA amplification was investigated for use in gene expression profiling experiments where starting material is limited. Yield and integrity of amplified antisense RNA (aaRNA), microarray hybridization intensities, and fidelity of differential gene expression detected were determined for arrays generated for unamplified versus amplified RNA from the same homogenous starting pools. Total RNA was extracted from bovine spleen and fetal ovary, serially diluted to concentrations ranging from 2 microg to 500 pg and amplified. Quality and quantity of total input RNA and aaRNA were assessed by spectrophotometry, gel electrophoresis and bioanalyzer. In experiment 1, we determined the optimal amounts of aaRNA generated from 20, 40, 200 ng and 2 microg input total RNA for use in cDNA synthesis, labeling and array hybridization that would yield robust and consistent hybridization signals on a bovine oocyte cDNA microarray. In experiment 2, comparison of microarray hybridization intensities and fidelity of differential gene expression between aaRNA generated from 2, 20 and 40 ng input total RNA versus unamplified RNA (uRNA) were conducted. The hybridization intensities for each of the 7000 spots per slide for microarrays conducted using aaRNA versus uRNA were highly correlated (2 ng = 0.84, 20 ng = 0.88, 40 ng = 0.90; P < 0.01). The false positive rate was low and similar (4.0% versus 4.4%) for arrays done with uRNA and aaRNA. Ninety-seven ESTs were detected as differentially expressed in the fetal ovary versus spleen at > 1.5- or < 0.5-fold using uRNA (P < 0.05). However, the number of genes detected in arrays using aaRNA was approximately 1.5-2.5 times greater than with uRNA. Approximately, 65-70% of differentially expressed genes were common between uRNA and aaRNA arrays. Relative fold-expression (Cy3/Cy5 ratios) for 25 overlapping abundant genes was comparable for uRNA versus aaRNA arrays with 2 and 20 ng total RNA as input. Results demonstrate that T7-based linear amplification of small amounts of input RNA and use of aaRNA in microarray experiments retains fidelity of detection of differential gene expression that is relatively comparable to experiments done with uRNA and provides a potentially viable approach to facilitate gene expression profiling using limited amounts of starting material.

Animals↗

PubMed2004

Generation of a bovine oocyte cDNA library and microarray: resources for identification of genes important for follicular development and early embryogenesis.

The oocyte is a key regulator of ovarian folliculogenesis and early embryonic development. However, the composition of the oocyte transcriptome and identities and functions of key oocyte-specific genes involved in the above processes are relatively unknown. Using a PCR-based cDNA amplification method (SMART technology), we constructed a bovine oocyte cDNA library. Analysis of 230 expressed sequence tags (ESTs) from this library identified 102 unique sequences. Although some correspond to housekeeping genes (e.g., ribosomal protein L15) and some represent genes previously known to be expressed in oocytes and other tissues, most encode for genes whose expression in mammalian oocytes has not been reported previously (e.g., cocaine- and amphetamine-regulated transcript) or genes of unknown function. Sixteen did not show significant sequence similarity to any entries in the GenBank database and were classified as novel. Using over 2,000 unsequenced, randomly selected cDNA clones from the library, we constructed an oocyte microarray and performed experiments to identify genes preferentially expressed in fetal ovary (an enriched source of oocytes) relative to somatic tissues. Eleven clones were identified by microarray analysis with consistently higher expression in fetal ovaries (collected from animals at days 210-260 of gestation) compared with spleen and liver. DNA sequence analysis of these clones revealed that two correspond to JY-1, a novel bovine oocyte-specific gene. The remaining nine clones represent five identified genes and one additional completely novel gene. Increased abundance of mRNA in fetal ovary for five of the six genes identified was confirmed by real-time PCR. Results demonstrate the potential utility of these unique resources for identification of oocyte-expressed genes potentially important for reproductive function.

Animals↗

PubMed2004

Evidence that cocaine- and amphetamine-regulated transcript is a novel intraovarian regulator of follicular atresia.

We recently obtained evidence that cocaine- and amphetamine-regulated transcript (CART), a potent anorectic neuropeptide, is expressed in the bovine ovary. The objectives of this study were to characterize bovine ovarian CART and determine its localization, regulation, and regulatory role during follicular development. CART mRNA was detected in stroma of adult ovaries and in large follicles, but was undetectable in several peripheral tissues, fetal ovaries, and corpora lutea. Within the ovary, CART mRNA and peptide were localized to the granulosal layer of some, but not all, antral follicles, with low, but detectable, expression in oocytes and cumulus cells. CART mRNA was undetectable in granulosal cells of dominant ovulatory follicles collected before and after the preovulatory gonadotropin surge, but was detected in the granulosal layer of adjacent subordinate follicles. In addition, amounts of CART mRNA and follicular fluid concentrations of CART peptide were greater in subordinate follicles vs. dominant follicles of the first follicular wave. Furthermore, CART treatment inhibited basal estradiol production, but not progesterone production, by granulosal cells in a dose-dependent fashion, and the effect was dependent on stage of cell differentiation. We conclude that granulosal cell CART expression is temporally regulated and potentially associated with follicle health status, and CART can inhibit granulosal cell estradiol production. Thus, CART may be a novel local regulator of follicular atresia in the bovine ovary.

Amino Acid Sequence↗

PubMed2004

Gonadotropin surge-induced differential upregulation of collagenase-1 (MMP-1) and collagenase-3 (MMP-13) mRNA and protein in bovine preovulatory follicles.

The ovulatory process is characterized by focalized extracellular matrix degradation at the apex of preovulatory follicles. Many studies have implicated the matrix metalloproteinases (MMPs) as potential mediators of follicle rupture. Objectives of this study were to determine localization and effect of the gonadotropin surge on temporal expression of MMP-1 and MMP-13 in bovine preovulatory follicles. Samples were collected at 0, 6, 12, 18, 24, and 48 h (corpora lutea) after GnRH injection (n = 5-6 per time point) and amounts of MMP-1 and MMP-13 mRNA and protein determined using dot blot or semiquantitative RT-PCR and Western blot analyses. Samples were also collected at 0 and 20 h after GnRH injection for immunohistochemical localization of MMP-1 and MMP-13. Results indicate that follicular expression of MMP-1 and MMP-13 increased following the gonadotropin surge. Abundance of MMP-1 mRNA increased at 6, 12, and 48 h post-GnRH injection. Immunoreactive MMP-1 was localized to granulosal and thecal layers of preovulatory follicles. Amounts of MMP-1 protein increased in both the apex and the base of preovulatory follicles. Abundance of MMP-13 mRNA increased at 6, 24, and 48 h post GnRH injection. Amounts of MMP-13 protein also increased in the follicular apex and base. Immunoreactive MMP-13 was localized to granulosal and thecal layers of preovulatory follicles. Results indicate MMP-1 and MMP-13 are increased in bovine preovulatory follicles following the gonadotropin surge but do not support a requirement for differential up-regulation of MMP-1 and MMP-13 (follicular apex vs. base) for the preovulatory collagenolysis required for follicle rupture.

Animals↗

PubMed2004

Mechanisms of glucocorticoid-induced down-regulation of neutrophil L-selectin in cattle: evidence for effects at the gene-expression level and primarily on blood neutrophils.

One anti-inflammatory action of glucocorticoids is down-regulation of surface L-selectin on circulating neutrophils. However, it is unclear if this is a result of release of affected bone marrow neutrophils or if the steroid has direct effects on L-selectin expression in existing blood neutrophils. We recently demonstrated that circulating neutrophils from cattle with high blood concentrations of endogenous glucocorticoid had reduced L-selectin mRNA, suggesting that the steroid interrupted L-selectin gene expression. In the current study, dexamethasone (DEX) was administered to cattle in vivo, and blood and bone marrow neutrophils were studied simultaneously within the animal to determine which pool of cells responds to glucocorticoids with inhibited L-selectin expression. Purified blood neutrophils were also treated with DEX +/- RU486 in vitro, and glucocorticoid effects on L-selectin expression were determined. Our results indicate that glucocorticoid-induced suppression of L-selectin, which accompanies neutrophilia, is likely mediated by direct effects of glucocorticoid receptor activation on intracellular reservoirs of L-selectin mRNA and protein in cattle, predominantly in blood neutrophils.

Animals↗

PubMed2004

Effect of lubricant type and concentration on the punch tip adherence of model ibuprofen formulations.

A model formulation, comprising ibuprofen and direct compression lactose (Tablettose 80) was used to assess the influence of two lubricants, magnesium stearate and stearic acid, on punch tip adherence. Lubricant concentrations were varied from 0.25% to 2% w/w. Formulations in the presence and absence of 0.5% w/w colloidal silica (Aerosil 200) were examined, to assess the influence of the glidant on the anti-adherent effects of the lubricants. Differential scanning calorimetry (DSC) was used to examine the effect of the lubricants on the melting temperature of ibuprofen. Tablets were compacted using a single punch tablet press at 10 kN using hard chrome-plated punches or at 40 kN using uncoated steel punches, tooling was 12.5-mm diameter in each case. The upper punch faces were characterized by obtaining Taylor Hobson Talysurf surface profiles. Following compaction, ibuprofen attached to the face was quantified by spectroscopy. At low concentrations of each lubricant, the levels of sticking observed were similar. Whilst sticking increased at magnesium stearate concentrations above 1%, sticking with stearic acid remained relatively constant at all concentrations. DSC revealed that the melting temperature of ibuprofen was lowered by the formation of eutectic mixtures with both lubricants. However, the onset temperature of melting and melting point were lowered to a greater extent with magnesium stearate compared with stearic acid. When using uncoated tooling at 40 kN, the deleterious effects of magnesium stearate on the tensile strength of the tablets also contributed to sticking. When using chrome-plated punches at 10 kN, the tensile strength reduction by the presence of magnesium stearate was less pronounced, as was the level of sticking.

Adhesiveness↗

PubMed2004

Effect of punch tip geometry and embossment on the punch tip adherence of a model ibuprofen formulation.

The sticking of a model ibuprofen-lactose formulation with respect to compaction force, punch tip geometry and punch tip embossment was assessed. Compaction was performed at 10, 25 or 40 kN using an instrumented single-punch tablet press. Three sets of 'normal' concave punches were used to evaluate the influence of punch curvature and diameter. The punches were 10, 11 and 12 mm in diameter, respectively. The 10-mm punch was embossed with a letter 'A' logo to assess the influence of an embossment on sticking. Flat-faced punches (12.5 mm) were used for comparison with the concave tooling. Surface profiles (Taylor Hobson Talysurf 120) of the upper punch faces were obtained to evaluate the surface quality of the tooling used. Following compaction, ibuprofen attached to the upper punch face was quantified by spectroscopy. Increasing punch curvature from flat-faced punches to concave decreased sticking. Altering punch diameter of the concave punches had no effect on sticking when expressed as microg mm(-2). The embossed letter 'A' logo increased sticking considerably owing to the probable concentration of shear stresses at the lateral faces of the embossed logo.

Adhesiveness↗

PubMed2004

Localization and temporal regulation of tissue inhibitors of metalloproteinases 3 and 4 in bovine preovulatory follicles.

The matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are potential regulators of the focalized extracellular matrix degradation required for ovulation. The objectives of the present study were to determine localization and temporal regulation of TIMP-3 and TIMP-4 mRNA and protein in bovine preovulatory follicles. Ovaries containing preovulatory follicles were collected at 0, 12 and 20 h after GnRH injection for real-time PCR quantification of TIMP-3 and TIMP-4 mRNAs and immunohistochemical localization studies. Additional samples collected at 0, 6, 12, 18 and 24 h post GnRH injection were subjected to Western analysis to determine temporal changes in TIMP-3 and TIMP-4 proteins in the apex and base of preovulatory follicles. Results indicate the gonadotropin surge regulates TIMP-3 and TIMP-4 expression. TIMP-3 and TIMP-4 mRNAs increased within 12 h after GnRH injection. TIMP-3 protein was localized to granulosal and thecal layers of preovulatory follicles and adjacent ovarian stroma, whereas TIMP-4 immunoreactivity was localized to granulosal and thecal cells and ovarian blood vessels. Amounts of TIMP-3 and TIMP-4 proteins in the follicular apex peaked within 12 h post GnRH injection and subsequently declined by 24 h. However, amounts of TIMP-3 and TIMP-4 proteins in the base were not elevated after GnRH administration. Results demonstrate that mRNA and protein for both TIMP-3 and TIMP-4 are increased in bovine preovulatory follicles following the gonadotropin surge. Coordinate expression of TIMPs and MMPs may help regulate the extracellular matrix remodeling characteristic of the ovulatory process.

Animals↗

PubMed2003

Development and testing of a high-density cDNA microarray resource for cattle.

A cDNA microarray resource has been developed with the goal of providing integrated functional genomics resources for cattle. The National Bovine Functional Genomics Consortium's (NBFGC) expressed sequence tag (EST) collection was established in 2001 to develop resources for functional genomics research. The NBFGC EST collection and microarray contains 18,263 unique transcripts, derived from many different tissue types and various physiologically important states within these tissues. The NBFGC microarray has been tested for false-positive rates using self-self hybridizations and was shown to yield robust results in test microarray experiments. A web-accessible database has been established to provide pertinent data related to NBFGC clones, including sequence data, BLAST results, and ontology information. The NBFGC microarray represents the largest cDNA microarray for a livestock species prepared to date and should prove to be a valuable tool in studying genome-wide gene expression in cattle.

Animals↗

PubMed2003

Sexually dimorphic neurocalcin expression in the developing zebra finch telencephalon.

Differential display RT-PCR was used on RNA isolated from the zebra finch telencephalon to identify gene products potentially involved in its development, including the sexually dimorphic nuclei responsible for song learning and production. A cDNA identified only in juvenile females was cloned and sequenced. It shares homology with neurocalcin, a calcium binding protein. Northern blots indicated three neurocalcin species. A 10.6 kb transcript was present in males and most females throughout development and in adulthood. Smaller 6.2 and 3.3 kb species were detected almost exclusively in females and primarily between posthatching days 18-25. In situ hybridization, using a probe that identified all three mRNA species, indicated a broad distribution in the telencephalon of both sexes, with particularly high levels in the song nucleus RA. Across regions examined, neurocalcin expression was enhanced in females compared to males, probably reflecting the presence of the two smaller transcripts. However, within RA, neurocalcin expression was statistically equivalent between the sexes. These data indicate that calcium signaling via neurocalcin may be involved in telencephalic development, but suggest that sexually dimorphic expression of this gene exists on a level too general to specifically regulate masculine or feminine development of song control regions. Neurocalcin might: broadly influence functional differentiation, including areas that are not morphologically distinct between the sexes; be a benign consequence of general dimorphisms, such as those due to sex chromosomes; or involve a compensatory mechanism, which allows function of the juvenile female telencephalon to equal that of males, despite fundamental physiological differences.

Amino Acid Sequence↗

PubMed2003

Mixing efficiency in side-vented coating equipment.

The purpose of this study was to evaluate tablet mixing within side-vented coating equipment by assessing the development of color uniformity during coating. A colorimetric method was used to evaluate the time for uniform coating for different mixing baffle systems at different scales of equipment. The influence of tablet size was also determined. The inclusion of rabbit ear baffles in the small-scale equipment reduced the time to achieve color uniformity by 20 minutes. The design of baffle influenced the time for uniform color with a mixing efficiency rank order of tubular > ploughshare > rabbit ear. Upon scale-up, the efficiency of mixing seen at development scale remained equivalent in terms of the influence of baffle design. The study into the influence of tablet size revealed the importance that the total batch surface area has on the time taken to achieve color uniformity, with 7-mm diameter tablets having a higher surface area for an equivalent volume of product and taking 15 to 20 minutes longer to achieve color uniformity than 16-mm diameter tablets.

Color↗

PubMed2003

Effects of surface roughness and chrome plating of punch tips on the sticking tendencies of model ibuprofen formulations.

The sticking of three model ibuprofen-lactose formulations with respect to compaction force and the surface quality of the upper punch were assessed. Compaction was performed at 10, 25 or 40 kN using an instrumented single-punch tablet press. Two sets of 12.5-mm flat-faced punches were used to evaluate the influence of surface quality. A third set of chrome-plated tooling was also used. Surface profiles (Taylor Hobson Talysurf 120) of the normal tooling upper punches indicated a large difference in quality. The punches were subsequently classified as old (Ra = 0.33 microm) or new (Ra = 0.04 microm) where Ra is the mean of all positive deviations from zero. Surface profiles of sample tablets were also obtained. Following compaction, ibuprofen attached to the face was quantified by spectroscopy. Punch surface roughness, compaction force and the blend composition were all significant factors contributing to sticking. Chrome plating of punch faces increased sticking at a low compaction force but decreased sticking at higher forces. Surface roughness of the tablets did not correlate with the corresponding data for sticking, indicating that this is not a suitable method of quantifying sticking.

Adhesiveness↗

PubMed2002

Urocortin-deficient mice show hearing impairment and increased anxiety-like behavior.

Urocortin is a member of the corticotropin-releasing hormone peptide family and is found in many discrete brain regions. The distinct expression pattern of urocortin suggests that it influences such behaviors as feeding, anxiety and auditory processing. To better define the physiological roles of urocortin, we have generated mice carrying a null mutation of the urocortin gene. Urocortin-deficient mice have normal basal feeding behavior and stress responses, but show heightened anxiety-like behaviors in the elevated plus maze and open-field tests. In addition, hearing is impaired in the mutant mice at the level of the inner ear, suggesting that urocortin is involved in the normal development of cochlear sensory-cell function. These results provide the first example of a function for any peptidergic system in hearing.

Acoustic Stimulation↗