Identification of the first homozygous 1-bp deletion in GDF9 gene leading to primary ovarian insufficiency by using targeted massively parallel sequencing.

Targeted massively parallel sequencing (TMPS) has been used in genetic diagnosis for Mendelian disorders. In the past few years, the TMPS has identified new and already described genes associated with primary ovarian insufficiency (POI) phenotype. Here, we performed a targeted gene sequencing to find a genetic diagnosis in idiopathic cases of Brazilian POI cohort. A custom SureSelectXT DNA target enrichment panel was designed and the sequencing was performed on Illumina NextSeq sequencer. We identified 1 homozygous 1-bp deletion variant (c.783delC) in the GDF9 gene in 1 patient with POI. The variant was confirmed and segregated using Sanger sequencing. The c.783delC GDF9 variant changed an amino acid creating a premature termination codon (p.Ser262Hisfs*2). This variant was not present in all public databases (ExAC/gnomAD, NHLBI/EVS and 1000Genomes). Moreover, it was absent in 400 alleles from fertile Brazilian women screened by Sanger sequencing. The patient's mother and her unaffected sister carried the c.783delC variant in a heterozygous state, as expected for an autosomal recessive inheritance. Here, the TMPS identified the first homozygous 1-bp deletion variant in GDF9. This finding reveals a novel inheritance pattern of pathogenic variant in GDF9 associated with POI, thus improving the genetic diagnosis of this disorder.

Malignant testicular germ cell tumors in postpubertal individuals with androgen insensitivity: prevalence, pathology and relevance of single nucleotide polymorphism-based susceptibility profiling.

STUDY QUESTION: What is the prevalence of malignant testicular germ cell tumors (TGCT) and its precursors, (pre-) germ cell neoplasia in situ (GCNIS), in late teenagers and adults who have androgen insensitivity syndrome (AIS) and the impact of an individual's genetic susceptibility to development of TGCT? SUMMARY ANSWER: No GCNIS or TGCT was diagnosed, but pre-GCNIS was identified in 14 and 10% of complete and partial AIS patients, respectively, and was associated with a higher genetic susceptibility score (GSS), with special attention for KITLG (rs995030) and ATFZIP (rs2900333). WHAT IS KNOWN ALREADY: Many adult women with AIS decline prophylactic gonadectomy, while data regarding the incidence, pathophysiology and outcomes of TGCT in postpubertal individuals with AIS are lacking. The relevance of genetic factors, such as single nucleotide polymorphisms (SNPs), in predisposing AIS individuals to TGCT is unknown. STUDY DESIGN, SIZE, DURATION: This multicenter collaborative study on prophylactically removed gonadal tissue was conducted in a pathology lab specialized in germ cell tumor biology. PARTICIPANTS/MATERIALS, SETTING, METHODS: Material from 52 postpubertal individuals with molecularly confirmed AIS (97 gonadal samples) was included; the median age at surgery was 17.5 (14-54) years. Immunohistochemical studies and high-throughput profiling of 14 TGCT-associated SNPs were performed. The main outcome measures were the prevalence of pre-GCNIS, GCNIS and TGCT, and its correlation with a GSS, developed based on the results of recent genome-wide association studies. MAIN RESULTS AND ROLE OF CHANCE: The earliest recognizable change preceding GCNIS, referred to as pre-GCNIS, was present in 14% of individuals with complete and 10% of those with partial AIS at a median age of 16 years. No GCNIS or invasive TGCT were found. The median GSS was significantly greater for those with, compared to those without, pre-GCNIS (P = 0.01), with an overlap between groups. Our data suggest important roles for risk alleles G at KITLG (rs995030) and C at ATFZIP (rs2900333), among the 14 studied TGCT-associated SNPs. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: A limited number of cases were included. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that the prevalence of pre-GCNIS in individuals with AIS beyond puberty is around 15%. Genetic susceptibility likely contributes to pre-GCNIS development in AIS but factors related to malignant progression remain unclear. Although data in older patients remain scarce, malignant progression appears to be a rare event, although the natural history of the premalignant lesion remains unknown. Therefore, the practice of routine prophylactic gonadectomy in adults with AIS appears questionable and the patient's preference, after having been fully informed, should be decisive in this matter. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by research grants from the Research Foundation Flanders (FWO) (to M.C.), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq G0D6713N) (to B.B.M. and M.C.) and the European Society for Pediatric Endocrinology (ESPE), granted by Novo Nordisk AB (to J.K.). There are no competing interests.

Effects of Type 1 Insulin-Like Growth Factor Receptor Silencing in a Human Adrenocortical Cell Line.

Type 1 insulin-like growth factor receptor (IGF-1R) is overexpressed in a variety of human cancers, including adrenocortical tumors. The aim of the work was to investigate the effects of IGF-1R downregulation in a human adrenocortical cell line by small interfering RNA (siRNA). The human adrenocortical tumor cell line NCI H295R was transfected with 2 specific IGF1R siRNAs (# 1 and # 2) and compared with untreated cells and a negative control siRNA. IGF1R expression was determined by quantitative reverse-transcription PCR (qRTPCR) and Western blot. The effects of IGF-1R downregulation on cell proliferation and apoptosis were assessed. IGF-1R levels were significantly decreased in cells treated with IGF-1R siRNA # 1 or # 2. Relative expression of IGF1R mRNA decreased approximately 50% and Western blot analysis revealed a 30% of reduction in IGF-1R protein. Downregulation of this gene resulted in 40% reduction in cell growth in vitro and 45% increase in apoptosis using siRNA # 2. These findings demonstrate that decreasing IGF-1R mRNA and protein expression in NCI H295R cells can partially inhibit adrenal tumor cell growth in vitro. Targeting IGF1R is a promising therapy for pediatric malignant adrenocortical tumor and can still be an option for adult adrenocortical cancer based on personalized genomic tumor profiling.

Job stress and temperaments in female nurses.

BACKGROUND: According to previous studies, temperament predicts a large share of the variance in job stress. It may be necessary for mental health practitioners to offer intervention strategies in accordance with individual temperament. AIMS: To investigate the relationship between job stress and temperament among nurses in a general hospital and to provide insight into personality traits influencing their mental or physical health. METHODS: A questionnaire survey of nurses in a general hospital. Work stress was measured using the Japanese version of the Effort-Reward Imbalance (ERI) scale. Temperament was assessed by a Japanese version of Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A). Hierarchical multiple regression analysis was used to determine the independent contribution of temperament to effort-reward ratio and over-commitment. RESULTS: Response rate was 48% (326/685). Temperament predicted part of the variance of the four ERI ratios (effort-reward ratio 26%; effort-esteem ratio 27%; effort-promotion ratio 26%; and effort-security ratio 18%) and also of over-commitment (38%). Depressive temperament influenced all four ERI ratios and over-commitment. Anxious temperament influenced only over-commitment. CONCLUSIONS: Nurses with depressive or anxious temperaments should be identified, monitored for signs of job stress and offered interventions to prevent adverse physical and mental effects.

Use of Drugs Considering Route of Administration on Drug Prescription Pattern for Bronchial Asthma in a Tertiary Level Hospital.

Bronchial asthma is one of the much known long-term respiratory conditions. Incidence is increasing, in developing countries like Bangladesh. Cross-sectional type of observational study was carried out over one year (July 2017 to June 2018) in the department of Pharmacology with collaboration of the department of Respiratory Medicine and Medicine, Mymensingh Medical College and Hospital, Mymensingh, Bangladesh. A total of 160 patients were selected non-randomly for the study. Inhalation route (52.35%) was the most preferred one over oral route (47.65%). In total 245 drugs, 131 FDC drugs (Salmeterol + Fluticasone) were prescribed with inhalation therapy which is 53.46%, another 9 FDC drugs that is (Ipratropium bromide + Salbutamol) were prescribed with inhalation therapy which is 3.67%, 101 drugs (Salbutamol) were prescribed with inhalation therapy that is 41.23%, 4 drugs (Beclomethasone) were prescribed with inhalation therapy that is 1.64%. Majority of patient were taking inhalation form of anti-asthmatic drugs.

A Narrative Review of Parameters Influencing Preeclampsia in the COVID-19 Era.

The COVID-19 outbreak has emerged as one of the most profound medical events of the 21st century, leaving an indelible impact on a global scale. The widespread prevalence causing significant illness and death needs collaborative and inventive efforts to deal with this challenge. One of the particular subset of the general population that had endured a significant impact was the pregnant population. A key complication of pregnancy seen in patients with a COVID-19 infection was the increased risk of developing preeclampsia. The angiotensin-converting enzyme 2 (ACE2) receptor is an important part of the renin-angiotensin system, which has been implicated in the control of blood flow and also is a key receptor in the pathogenesis of the multitude of symptoms of COVID-19. This study aimed to evaluate the psychiatric, hematological, neurological, and social factors influenced by the COVID-19 virus and its subsequent effect on the development of preeclampsia. Increased rates of anxiety and depression were seen globally during the COVID-19 pandemic and due to the following physiological response of anxiety and depression, elevated blood pressure levels and development of preeclampsia were noted. Neurological factors such as the development of posterior reversible encephalopathy syndrome and its relationship between COVID-19 and preeclampsia were also strongly observed. The observation suggested biomarkers such as serum neurofilament light may be used as a screening tool to stratify the severity of preeclampsia. Hematological parameters observed were most notable for the presence of thrombocytopenia, which itself is a marker of the severity of preeclampsia. The numerous effects of COVID-19 on preeclampsia have proven to have a tremendous impact on the healthcare burden. Careful analysis and prevention strategies, if implemented, will contribute to reducing the morbidity and mortality of patients with preeclampsia and COVID-19 infections.

Factors in the Development of Somatoform Disorders Among Children: A Case-Control Study.

Introduction Somatoform disorders (SFDs) are a spectrum of diseases mainly manifesting with physical symptoms of no recognizable etiology. These disorders are believed to be primarily influenced and exacerbated by psychological factors. Given the connection between parental sociodemographics and psychological factors and SFDs, there is a pressing need to investigate this area further, particularly concerning parents and their children affected by somatoform disorders. Aims and objectives The aims and objectives of this study are as follows: i) study the determinants of SFDs, namely, parent handling of child, parent-child relationship, parenting with respect to attending to the needs of children, and intelligence quotient (IQ) of parents, and ii) compare host factors to the factors matched in control subjects. Materials and methods We adopted purposive sampling in our case-control study. The study sample was obtained from the psychiatry department of the Ganesh Shankar Vidyarthi Memorial (GSVM) Medical College, Kanpur, India, from September 2020 to December 2022, once a week, every Monday. Children manifesting SFD manifestations that are among the chief complaints were included in our study. Results A total of 115 cases were included in our study based on inclusion criteria. The study compared sociodemographic characteristics, intelligence quotient (IQ), parental characteristics, parental handling, parent-child relationships, and parenting practices between a patient group and a control group. The results showed no significant differences in sex, religion, occupation, domicile, and socioeconomic status in both control and patient groups. However, significant differences were found in parental characteristics, such as lower mean age, education, and IQ, in the patient group. This difference between the patient and control groups with respect to the parental handling questionnaire was statistically significant for the domain of "praise," "talk," "feel better," "comes to you," "unduly strict" items, "frequently reprimanded," "tried to control everything," creative activities, protectiveness, education, neglecting, objective punishment, housing, medical care, demanding, symbolic reward, loving, objective reward, food, parent-to-child communication, clothing, support, routine, recreation, social activities, rules, managing problem behavior, guidance for career, and security. Conclusion Parents were deficient in terms of years of education, occupational status, IQ, parental handling, parent-child relationship, and parenting with respect to the children's needs. These findings offer insights into the sociodemographic and psychological factors contributing to the patient group's condition.

Interaction of Eating Status and Dietary Variety on Incident Functional Disability among Older Japanese Adults.

OBJECTIVES: To examine whether eating status and dietary variety were associated with functional disability during a 5-year follow-up analysis of older adults living in a Japanese metropolitan area. DESIGN: A 5-year follow-up study. SETTING: Ota City, Tokyo, Japan. PARTICIPANTS: A total of 10,308 community-dwelling non-disabled adults aged 65-84 years. MEASUREMENTS: Eating status was assessed using a self-reported questionnaire. Dietary variety was assessed using the dietary variety score (DVS). Based on the responses, participants were classified according to eating alone or together and DVS categories (low: 0-3; high: 4-10). Functional disability incidence was prospectively identified using the long-term care insurance system's nationally unified database. Multilevel survival analyses calculated the adjusted hazard ratio (HR) and 95% confidence interval (CI) for incident functional disability. RESULTS: During a 5-year follow-up, 1,991 (19.3%) individuals had functional disabilities. Eating status or DVS were not independently associated with incident functional disability. However, interaction terms between eating status and DVS were associated with functional disability; HR (95% CI) for eating together and low DVS was 1.00 (0.90-1.11), eating alone and high DVS was 0.95 (0.77-1.17), and eating alone and low DVS was 1.20 (1.02-1.42), compared to those with eating together and high DVS. CONCLUSION: Older adults should avoid eating alone or increase dietary variety to prevent functional disability. This can be ensured by providing an environment of eating together or food provision services for eating a variety of foods in the community.

A notable case report of May-Hegglin anomaly with immune complex-related nephropathy: a genetic and histological analysis.

May-Hegglin anomaly (MHA) is a rare autosomal dominant disease characterized by macrothrombocytopenia and leukocyte inclusions with microfilaments in the ribosomes. Mutations in the MYH9 gene, encoding non-muscle myosin heavy chain IIA (NMMHC-IIA) have been identified in patients with MHA and other MYH9-related diseases. Two young males (an older and younger brother) presented with macrothrombocytopenia and leukocyte inclusion bodies. Electron microscopy (EM) revealed parallel filaments in leukocyte inclusion bodies characteristic of MHA. Immunofluorescence microscopy (IF) showed NMMHC-IIA antibodies in 1 - 2 leukocyte inclusion bodies. These findings were consistent with MHA and they were identified to express the MYH9 mutation, D1424H. The older brother underwent a renal biopsy because of persistent proteinuria. Histology revealed mesangial proliferative glomerulonephritis with granular deposits of IgG and C1q. EM showed that the dense deposits were located in subendothelial cells, mesangial cells and Bowman's capsule. Immunocytochemistry revealed that NMMHC-IIA antibodies were localized in podocyte and endothelial cells in the glomerulus. Moreover, the expression of nephrin and podocin, slit diagram protein, was normal. An inflammatory mechanism may occur separately from MYH9-related disease. This report presents a case of MHA with immune complex-related nephropathy.

Expansion of natural killer cells but not T cells in human interleukin 2/interleukin 2 receptor (Tac) transgenic mice.

Transgenic mice expressing both human IL-2 and the L chain of IL-2-R constitutively had an unusual expansion of Thy-1+/CD3-4-8- large granular lymphocytes, which bore the elevated NK activity. Unexpectedly, the transgenic mice had neither T cell expansion nor autoreactive antibodies. The increase in number and activity of NK cells seems to be responsible for both the severe interstitial pneumonia and lymphocyte depletion in the spleen that we found in these transgenic mice. In addition, we found the selective loss of Purkinje cells in the cerebellum of the mice, which gave rise to their disturbed gait. All the transgenic mice died by 4 wk of age.

Effort-reward imbalance and depressive state in nurses.

BACKGROUND: The mental health of nurses is an important issue. AIMS: To examine relationships between effort-reward imbalance (ERI) and depression and anxiety in nurses of a Japanese general hospital. METHODS: A self-report survey was conducted among 406 nurses. Work stress was measured using a Japanese version of the ERI scale. Depression and anxiety were assessed by an item of the QOL-26. Logistic regression analysis was used to determine the independent contribution of the effort-reward ratios or overcommitment to the depressive state. RESULTS: Both higher effort-money ratio and higher overcommitment significantly correlated with the depressive state (OR: 2.75; 95% CI: 1.34-5.66 and OR: 1.27; 95% CI: 1.15-1.41, respectively). CONCLUSIONS: These findings suggest that in addition to effort-money ratio, overcommitment at work is an especially important issue that may be able to be managed in health promotion services for nurses in general hospitals.

Abnormal features in skeletal muscle from mice lacking mitsugumin29.

Physiological roles of the members of the synaptophysin family, carrying four transmembrane segments and being basically distributed on intracellular membranes including synaptic vesicles, have not been established yet. Recently, mitsugumin29 (MG29) was identified as a novel member of the synaptophysin family from skeletal muscle. MG29 is expressed in the junctional membrane complex between the cell surface transverse (T) tubule and the sarcoplasmic reticulum (SR), called the triad junction, where the depolarization signal is converted to Ca(2+) release from the SR. In this study, we examined biological functions of MG29 by generating knockout mice. The MG29-deficient mice exhibited normal health and reproduction but were slightly reduced in body weight. Ultrastructural abnormalities of the membranes around the triad junction were detected in skeletal muscle from the mutant mice, i.e., swollen T tubules, irregular SR structures, and partial misformation of triad junctions. In the mutant muscle, apparently normal tetanus tension was observed, whereas twitch tension was significantly reduced. Moreover, the mutant muscle showed faster decrease of twitch tension under Ca(2+)-free conditions. The morphological and functional abnormalities of the mutant muscle seem to be related to each other and indicate that MG29 is essential for both refinement of the membrane structures and effective excitation-contraction coupling in the skeletal muscle triad junction. Our results further imply a role of MG29 as a synaptophysin family member in the accurate formation of junctional complexes between the cell surface and intracellular membranes.

Deficiency of triad junction and contraction in mutant skeletal muscle lacking junctophilin type 1.

In skeletal muscle excitation-contraction (E-C) coupling, the depolarization signal is converted from the intracellular Ca2+ store into Ca2+ release by functional coupling between the cell surface voltage sensor and the Ca2+ release channel on the sarcoplasmic reticulum (SR). The signal conversion occurs in the junctional membrane complex known as the triad junction, where the invaginated plasma membrane called the transverse-tubule (T-tubule) is pinched from both sides by SR membranes. Previous studies have suggested that junctophilins (JPs) contribute to the formation of the junctional membrane complexes by spanning the intracellular store membrane and interacting with the plasma membrane (PM) in excitable cells. Of the three JP subtypes, both type 1 (JP-1) and type 2 (JP-2) are abundantly expressed in skeletal muscle. To examine the physiological role of JP-1 in skeletal muscle, we generated mutant mice lacking JP-1. The JP-1 knockout mice showed no milk suckling and died shortly after birth. Ultrastructural analysis demonstrated that triad junctions were reduced in number, and that the SR was often structurally abnormal in the skeletal muscles of the mutant mice. The mutant muscle developed less contractile force (evoked by low-frequency electrical stimuli) and showed abnormal sensitivities to extracellular Ca2+. Our results indicate that JP-1 contributes to the construction of triad junctions and that it is essential for the efficiency of signal conversion during E-C coupling in skeletal muscle.

Antibacterial Effect of Aloe vera (Aloe barbadensis) leaf gel against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae.

This experimental study was carried out to determine the antibacterial effect of Ethanolic extract of Aloe vera leaf gel (EAE) against standard strains of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae in the Department of Pharmacology & Therapeutics in collaboration with the Department of Microbiology, Mymensingh Medical College, Mymensingh, Bangladesh from July 2017 to June 2018. Ethanol extract was used in five different concentrations (100, 200, 300, 400 and 500µg/ml). Dose dependent inhibitory effect was seen against the test organisms using disc diffusion method. For S. aureus, Zones of inhibition (ZOI) were 7, 12, 13, 16 and 20 mm at 100, 200, 300, 400 and 500 µg/ml respectively; for P. aeruginosa, ZOI were 0, 7, 12, 14 and 17 mm at 100, 200, 300, 400 and 500 µg/ml respectively; for E. coli, ZOI were 0, 8, 12, 15 and 18 mm at 100, 200, 300, 400 and 500 µg/ml respectively; for K. pneumoniae, ZOI were 7, 10, 11, 13 and 17 mm at 100, 200, 300, 400 and 500 µg/ml respectively. The minimum inhibitory concentration (MIC) was assessed by broth dilution technique. The MICs of EAE for S. aureus, P. aeruginosa, E. coli and K. pneumoniae were 500, 650, 650 and 600 µg/ml respectively. From the study it is clearly observed that ethanolic extract of Aloe vera leaf gel possesses antibacterial effect against the test pathogens. Further studies are required to detect and isolate the biologically active ingredients present in the Aloe vera leaves which are responsible for this antibacterial effect. Hopefully, that would lead to the discovery of new and more potent antimicrobial agents originated from Aloe vera.

Score-Based and Nutrient-Derived Dietary Patterns Are Associated with Depressive Symptoms in Community-Dwelling Older Japanese: A Cross-Sectional Study.

OBJECTIVES: This study evaluated associations of score-based and nutrient-derived dietary patterns with depressive symptoms in community-dwelling older Japanese. DESIGN: Cross-sectional study. SETTING: Community-based. PARTICIPANTS: 982 community-dwelling adults aged 65 years or older. MEASUREMENTS: Score-based pattern was assessed by using dietary variety score (DVS), which covers 10 food group items in Japanese meals. Nutrient-derived dietary patterns were identified by using reduced rank regression (RRR), with folate, vitamin C, magnesium, calcium, iron, and zinc intakes as response variables. Depressive symptoms were assessed with the Geriatric Depression Scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for these dietary patterns in multivariate logistic regression analyses with potential confounders. The lowest consumption category was used as the reference group. RESULTS: The prevalence of depressive symptoms was 13.5%. Higher DVS was associated with fewer depressive symptoms (OR=0.52, 95% CI=0.27-1.03 for the highest vs the lowest DVS; P for trend=0.031). The first RRR dietary pattern score was characterized by high intakes of fish, soybean products, potatoes, most vegetables, mushrooms, seaweeds, fruits, and green tea and a low intake of rice and was inversely associated with the prevalence of depressive symptoms (OR=0.53, 95% CI=0.30-0.92; P for trend=0.030). CONCLUSION: Greater dietary variety and a dietary pattern characterized by high intakes of fish, soybean products, potatoes, most vegetables, mushrooms, seaweeds, fruit, and green tea and a low intake of rice were consistently associated with lower prevalence of depressive symptoms in community-dwelling older Japanese. Therefore, both patterns identified the components of dietary habits essential to depression prevention.

Last resort for renal transplant recipients, 'restored kidneys' from living donors/patients.

Because of the grave shortage of deceased kidney allografts in Japan, we have embarked on a new source of organs, 'Restored kidneys' from living patients. From January 1991 through September 2006, 42 kidneys (eight benign pathology, eight small renal cancers, eight ureteral cancers, six aneurysms, eight severe nephrotic syndrome from four patients and four ureteral stenosis) were obtained from 38 patients/donors after extensive discussion of treatment modalities and risks. All patients/donors agreed to undergo total nephrectomy. The lesions were removed/repaired ex vivo on the back table, then transplanted. All recipients were notified of all possible risks including donor disease recurrence. One, 5 and 10-year patient survival rates of restored transplant patients were 92.9%, 79.3% and 63.8%, respectively. One, 5 and 10-year graft survival rates of restored kidney transplant patients were 78.6%, 51.8% and 42.7%, respectively. There were no recurrences of small renal cell carcinomas. There was one recurrence of ureteral cancer in the transplanted kidney 15 months after operation. In countries where deceased donors are scarce, such as Japan, the restored kidneys can be a last resort for renal allografts.

Regional distribution of importin subtype mRNA expression in the nervous system: study of early postnatal and adult mouse.

Importin-alpha and beta1 mediate the translocation of macromolecules bearing nuclear localization signals across the nuclear pore complex. Five importin-alpha isoforms have been identified in mice and six in human. Some of these importins play an important role in neural activity such as long term potentiation, but the functional differences of each isoform in the CNS are still unclear. We performed in situ hybridization (ISH) using non-isotopic probes to clarify the expression patterns of importin-alpha subtypes (alpha5, alpha7, alpha1, alpha4, alpha3) and importin-beta1 in the mouse CNS of adult and early postnatal stages. The mRNAs of the importin-alpha subtypes and importin beta1 were expressed throughout the CNS with specific patterns; importin-alpha5, alpha7, alpha3, and beta1 showed moderate to high expression levels throughout the brain and spinal cord; importin-alpha4 showed a lack of expression in limited regions; and importin-alpha1 showed a low expression level throughout the brain and spinal cord but with a moderate expression level in the olfactory bulb and reticular system. We also demonstrated that importin-alphas and beta1 mRNAs were predominantly expressed in neurons in the adult mouse brain by using double-labeling fluorescence ISH and immunohistochemistry. Moreover, importin-alphas and beta1 mRNAs were detected throughout the CNS of postnatal mice and were highly expressed in the external granule layer of the cerebellar cortex on postnatal days 0, 4, and 10. This is the first report of importin-alphas and beta1 expression throughout the CNS of adult mice, as well as in the developing brain, including cell type specific localization.