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Lijun Feng - One of the best experts on this subject based on the ideXlab platform.
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the mutation of the AP3B1 gene causes uterine hypoplasia in pearl mice
Reproductive Sciences, 2020Co-Authors: Renwei Jing, Haiqing Zhang, Yu Kong, Xuan Dong, Jie Yan, Jia Han, Gang Han, Jingye Zhang, Lijun FengAbstract:The pearl (pe) mouse mutant has been identified as a model for Hermansky-Pudlak syndrome and bears a mutation in the beta3A subunit of the AP-3 complex, which has a core function in the biogenesis and function of various lysosomal-related organelles. Through large-scale mating, we found that female pearl mice also displayed reduced fertility with a smaller litter size. Abnormal uteri in both 1-month-old and 3-month-old mice were observed as having short and thin uterine horns, indicating abnormal development. Histological studies revealed that the endometrial epithelium and endometrial stoma of the uterus were both thinner than those in the normal controls. We examined some key factors in uterine development, including the Hoxa10, Hoxa11, and Wnt5a genes, and found that they all presented lower mRNA and protein levels. The pearl mouse could serve as a model for uterine hypoplasia, a common problem in female infertility.
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Different functions of biogenesis of lysosomal organelles complex 3 subunit 1 (Hps1) and adaptor-related protein complex 3, beta 1 subunit (AP3B1) genes on spermatogenesis and male fertility.
Reproduction fertility and development, 2019Co-Authors: Renwei Jing, Haiqing Zhang, Yu Kong, Xuan Dong, Jie Yan, Jia Han, Lijun FengAbstract:Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder in humans and mice. Pale ear (ep) and pearl (pe) mice, bearing mutations in the biogenesis of lysosomal organelles complex 3 subunit 1 (Hps1) and adaptor-related protein complex 3, beta 1 subunit (AP3B1) genes respectively, are mouse models of human HPS Type 1 (HPS1) and Type 2 (HPS2) respectively. In the present study we investigated and compared the reduced fertilities of ep and pe male mice. Both ep and pe males exhibited lower abilities to impregnate C57BL/6J (B6) females, and B6 females mated with ep males produced smaller litters than those mated with pe males. Delayed testis development, reduced sperm count and lower testosterone concentrations were observed in the pe but not ep male mice. However, the reduction in sperm motility was greater in ep than pe males, likely due to the mitochondrial and fibrous sheath abnormalities observed by electron microscopy in the sperm tails of ep males. Together, the results indicate that the Hps1 and AP3B1 genes play distinct roles in male reproductive system development and spermatogenesis in mice, even though ep and pe males share common phenotypes, including reduced lysosomes in Sertoli cells and dislocated Zn2+ in sperm heads.
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The AP3B1 gene regulates the ocular melanosome biogenesis and tyrosinase distribution differently from the Hps1 gene
Experimental eye research, 2014Co-Authors: Renwei Jing, Xuan Dong, Jie Yan, Xiangyuan Chen, Lijun FengAbstract:Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder in humans and mice. The pearl (pe) mouse, a mouse model for the human HPS-2, bears a mutation in AP3B1 gene. Here we investigated the pigmentation in eyes of pearl (pe) mice, and compared it with our previously published data in pale ear (ep) mice. We revealed that the hypopigmentation in eyes of pearl mice was more severe than pale ear mice, especially in the neural crest-derived tissues. However, the total tyrosinase activity in eyes of pearl mice was stronger than pale ear mice, suggesting that the degradation of aberrantly transported tyrosinase in eyes of pearl mice was weaker than that of pale ear mice. Furthermore, the pigmentation in eyes of mice doubly heterozygous for Hps1 and AP3B1 genes was similar to the wild-type, while the hypopigmentation in iris of double mutant mice was more severe than either single mutant. Besides, we found several previously reported characters in pale ear mice, including macromelanosomes in the neural crest-derived melanocytes and increased accumulation of lipofuscin in the RPE, were absent in pearl mice. Our study indicates that AP3B1 gene play distinct roles in melanin production and tyrosinase distribution compared with Hps1 gene.
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genomic structure of the mouse AP3B1 gene in normal and pearl mice
Genomics, 2000Co-Authors: Lijun Feng, Brian W Rigatti, Edward K Novak, Michael B Gorin, Richard T SwankAbstract:The mouse hypopigmentation mutant pearl is an established model for Hermansky-Pudlak syndrome (HPS), a genetically heterogenous disease with misregulation of the biogenesis/function of melanosomes, lysosomes, and platelet dense granules. The pearl (AP3B1) gene encodes the beta3A subunit of the AP-3 adaptor complex, which regulates vesicular trafficking. The genomic structure of the normal AP3B1 gene includes 25 introns and a putative promoter sequence. The original pearl (pe) mutation, which has an unusually high reversion rate on certain strain backgrounds, has been postulated to be caused by insertion of a transposable element. Indeed, the mutation contains a 215-bp partial mouse transposon at the junction point of a large tandem genomic duplication of 6 exons and associated introns. At the cDNA level, three pearl mutations (pearl, pearl-8J, and pearl-9J) are caused by deletions or duplications of a complete exon(s).
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the beta3a subunit gene AP3B1 of the ap 3 adaptor complex is altered in the mouse hypopigmentation mutant pearl a model for hermansky pudlak syndrome and night blindness
Human Molecular Genetics, 1999Co-Authors: Lijun Feng, Edward K Novak, Albert B Seymour, Shelley Jiang, Andrew A Peden, Lijie Zhen, Michael E Rusiniak, Eva M Eicher, Margaret S Robinson, Michael B GorinAbstract: 1999 Oxford University Press Human Molecular Genetics, 1999, Vol. 8, No. 2 The β3A subunit gene (AP3B1) of the AP-3 adaptor complex is altered in the mouse hypopigmentation mutant pearl, a model for Hermansky–Pudlak syndrome and night blindness Lijun Feng + , Albert B. Seymour 1,+ , Shelley Jiang , Agnes To 2 , Andrew A. Peden 3 , Edward K. Novak , Lijie Zhen , Michael E. Rusiniak , Eva M. Eicher 4 , Margaret S. Robinson 3 , Michael B. Gorin 2 and Richard T. Swank* Department of Molecular and Cell Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA, 1 Pfizer Central Research, Department of Genomics, Targets and Cancer, Eastern Point Road, Groton, CT 06340, USA, 2 Department of Human Genetics and Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15213, USA, 3 University of Cambridge, Department of Clinical Biochemistry, Cambridge CB2 2QR, UK and 4 The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA Received September 18, 1998; Revised and Accepted November 6, 1998 Lysosomes, melanosomes and platelet-dense granules are abnormal in the mouse hypopigmentation mutant pearl. The β3A subunit of the AP-3 adaptor complex, which likely regulates protein trafficking in the trans- Golgi network/endosomal compartments, was iden- tified as a candidate for the pearl gene by a positional/ candidate cloning approach. Mutations, including a large internal tandem duplication and a deletion, were identified in two respective pearl alleles and are pre- dicted to abrogate function of the β3A protein. Signifi- cantly lowered expression of altered β3A transcripts occurred in kidney of both mutant alleles. The several distinct pearl phenotypes suggest novel functions for the AP-3 complex in mammals. These experiments also suggest mutations in AP-3 subunits as a basis for unique forms of human Hermansky–Pudlak syndrome and congenital night blindness, for which the pearl mouse is an appropriate animal model. INTRODUCTION The autosomal recessive mouse mutation pearl (pe) (1) maps to distal chromosome 13 (2–4). Pearl mice are appropriate models for Hermansky–Pudlak syndrome (HPS) as they exhibit hypo- pigmentation, lysosomal secretion abnormalities and platelet- dense granules with reduced levels of adenine nucleotides and serotonin (5). The latter leads to the prolonged bleeding symptomatic of platelet storage pool deficiency and HPS. Additionally, pearl mice exhibit reduced sensitivity in the dark-adapted state, suggesting a model for human congenital stationary night blindness (6). HPS patients have altered biosynthesis/function of melanosomes, platelet-dense granules and lysosomes (7–9). Due to associated fibrotic lung disease, prolonged bleeding and colitis, HPS leads to high morbidity and increased mortality (8–10) in the third to fifth decades of life. It occurs in diverse populations worldwide and is especially prevalent in selected regions such as Puerto Rico, due to founder effects. No curative therapies exist. Intracellular protein sorting and trafficking are conducted by means of carrier vesicles (11) whose formation is mediated by adaptor protein (AP) complexes (12). An adaptor-related coat complex, termed AP-3, likely facilitates trafficking of vesicles from the trans-Golgi network and/or endosomal compartments by interacting with tyrosine and di-leucine signals on proteins of lysosomes and other intracellular organelles (13,14). AP-3 is heterotetrameric containing two large subunits, δ and β3, a medium subunit, µ3, and a small subunit, σ3. Details of the function of AP-3 in mammals are not well understood. We report positional/candidate cloning of pearl and evidence from mutational analysis that the primary pearl gene defect is in the β3A subunit (the AP3B1 gene) of the AP-3 adaptor complex. RESULTS Positional/candidate cloning identifies β3A as a candidate gene for pearl Identification of β3A as a candidate for the pearl (pe) gene required high resolution genetic and physical maps. We previously localized pe to a 0.5 cM region (2,3) on chromosome 13 between D13Mit28/29 and Cf2r using an interspecific backcross of 1250 progeny. Further analyses (Fig. 1A) showed that D13Mit28 is *To whom correspondence should be addressed. Tel: +1 716 845 3429; Fax: +1 716 845 8169; Email: rswank@mcbio.med.buffalo.edu + These two authors contributed equally to this study
Subarna Chakravorty - One of the best experts on this subject based on the ideXlab platform.
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disruption of AP3B1 by a chromosome 5 inversion a new disease mechanism in hermansky pudlak syndrome type 2
BMC Medical Genetics, 2013Co-Authors: Matthew L Jones, Sherina L Murden, Claire Brooks, Viv K Maloney, Richard A Manning, Kimberly Gilmour, Vandana Bharadwaj, Josu De La Fuente, Subarna ChakravortyAbstract:Background Hermansky-Pudlak syndrome 2 (HPS2; OMIM #608233) is a rare, autosomal recessive disorder caused by loss-of-function genetic variations affecting AP3B1, which encodes the β3A subunit of the adaptor-related protein complex 3 (AP3). Phenotypic characteristics include reduced pigmentation, absent platelet dense granule secretion, neutropenia and reduced cytotoxic T lymphocyte (CTL) and natural killer (NK) cell function. To date HPS2 has been associated with non-synonymous, stop-gain or deletion-insertion nucleotide variations within the coding region of AP3B1.
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disruption of AP3B1 by a chromosome 5 inversion a new disease mechanism in hermansky pudlak syndrome type 2
BMC Medical Genetics, 2013Co-Authors: Matthew L Jones, Sherina L Murden, Claire Brooks, Viv K Maloney, Richard A Manning, Kimberly Gilmour, Vandana Bharadwaj, Josu De La Fuente, Subarna ChakravortyAbstract:Hermansky-Pudlak syndrome 2 (HPS2; OMIM #608233) is a rare, autosomal recessive disorder caused by loss-of-function genetic variations affecting AP3B1, which encodes the β3A subunit of the adaptor-related protein complex 3 (AP3). Phenotypic characteristics include reduced pigmentation, absent platelet dense granule secretion, neutropenia and reduced cytotoxic T lymphocyte (CTL) and natural killer (NK) cell function. To date HPS2 has been associated with non-synonymous, stop-gain or deletion-insertion nucleotide variations within the coding region of AP3B1. We describe a consanguineous female infant with reduced pigmentation, neutropenia and recurrent infections. Platelets displayed reduced aggregation and absent ATP secretion in response to collagen and ADP, indicating a platelet dense granule defect. There was increased basal surface expression of CD107a (lysosome-associated membrane protein 1(LAMP-1)) on NK cells and CTLs from the study subject and a smaller increase in the percentage of CD107a positive cells after stimulation compared to most healthy controls. Immunoblotting of protein extracts from EBV-transformed lymphoblasts from the index case showed absent expression of full-length AP-3 β3A subunit protein, confirming a phenotypic diagnosis of HPS2. The index case displayed a homozygous pericentric inv(5)(p15.1q14.1), which was also detected as a heterozygous defect in both parents of the index case. No loss of genetic material was demonstrated by microarray comparative genome hybridisation at 60kb resolution. Fluorescence in-situ hybridisation using the 189.6kb probe RP11-422I12, which maps to 5q14.1, demonstrated dual hybridisation to both 5q14.1 and 5p15.1 regions of the inverted Chr5. The RP11-422I12 probe maps from intron 1 to intron 16 of AP3B1, thus localising the 5q inversion breakpoint to within AP3B1. The probe RP11-211K15, which corresponds to an intergenic region on 5p also showed dual hybridisation, enabling localisation of the 5p inversion breakpoint. This case report extends the phenotypic description of the very rare disorder HPS2. Our demonstration of a homozygous Chr5 inversion predicted to disrupt AP3B1 gene provides a novel pathogenic mechanism for this disorder.
B. Wildemann - One of the best experts on this subject based on the ideXlab platform.
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‘Medusa head ataxia’: the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 2: Anti-PKC-gamma, anti-GluR-delta2, anti-Ca/ARHGAP26 and anti-VGCC
Journal of Neuroinflammation, 2015Co-Authors: S. Jarius, B. WildemannAbstract:Serological testing for anti-neural autoantibodies is important in patients presenting with idiopathic cerebellar ataxia, since these autoantibodies may indicate cancer, determine treatment and predict prognosis. While some of them target nuclear antigens present in all or most CNS neurons (e.g. anti-Hu, anti-Ri), others more specifically target antigens present in the cytoplasm or plasma membrane of Purkinje cells (PC). In this series of articles, we provide a detailed review of the clinical and paraclinical features, oncological, therapeutic and prognostic implications, pathogenetic relevance, and differential laboratory diagnosis of the 12 most common PC autoantibodies (often referred to as ‘Medusa head antibodies’ due their characteristic somatodendritic binding pattern when tested by immunohistochemistry). To assist immunologists and neurologists in diagnosing these disorders, typical high-resolution immunohistochemical images of all 12 reactivities are presented, diagnostic pitfalls discussed and all currently available assays reviewed. Of note, most of these antibodies target antigens involved in the mGluR1/calcium pathway essential for PC function and survival. Many of the antigens also play a role in spinocerebellar ataxia. Part 1 focuses on anti-metabotropic glutamate receptor 1-, anti-Homer protein homolog 3-, anti-Sj/inositol 1,4,5-trisphosphate receptor- and anti-carbonic anhydrase-related protein VIII-associated autoimmune cerebellar ataxia (ACA); part 2 covers anti-protein kinase C gamma-, anti-glutamate receptor delta-2-, anti-Ca/RhoGTPase-activating protein 26- and anti-voltage-gated calcium channel-associated ACA; and part 3 reviews the current knowledge on anti-Tr/delta notch-like epidermal growth factor-related receptor-, anti-Nb/AP3B2-, anti-Yo/cerebellar degeneration-related protein 2- and Purkinje cell antibody 2-associated ACA, discusses differential diagnostic aspects, and provides a summary and outlook.
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medusa head ataxia the expanding spectrum of purkinje cell antibodies in autoimmune cerebellar ataxia part 1 anti mglur1 anti homer 3 anti sj itpr1 and anti carp viii
Journal of Neuroinflammation, 2015Co-Authors: S. Jarius, B. WildemannAbstract:Serological testing for anti-neural autoantibodies is important in patients presenting with idiopathic cerebellar ataxia, since these autoantibodies may indicate cancer, determine treatment and predict prognosis. While some of them target nuclear antigens present in all or most CNS neurons (e.g. anti-Hu, anti-Ri), others more specifically target antigens present in the cytoplasm or plasma membrane of Purkinje cells (PC). In this series of articles, we provide a detailed review of the clinical and paraclinical features, oncological, therapeutic and prognostic implications, pathogenetic relevance, and differential laboratory diagnosis of the 12 most common PC autoantibodies (often referred to as ‘Medusa-head antibodies’ due to their characteristic somatodendritic binding pattern when tested by immunohistochemistry). To assist immunologists and neurologists in diagnosing these disorders, typical high-resolution immunohistochemical images of all 12 reactivities are presented, diagnostic pitfalls discussed and all currently available assays reviewed. Of note, most of these antibodies target antigens involved in the mGluR1/calcium pathway essential for PC function and survival. Many of the antigens also play a role in spinocerebellar ataxia. Part 1 focuses on anti-metabotropic glutamate receptor 1-, anti-Homer protein homolog 3-, anti-Sj/inositol 1,4,5-trisphosphate receptor- and anti-carbonic anhydrase-related protein VIII-associated autoimmune cerebellar ataxia (ACA); part 2 covers anti-protein kinase C gamma-, anti-glutamate receptor delta-2-, anti-Ca/RhoGTPase-activating protein 26- and anti-voltage-gated calcium channel-associated ACA; and part 3 reviews the current knowledge on anti-Tr/delta notch-like epidermal growth factor-related receptor-, anti-Nb/AP3B2-, anti-Yo/cerebellar degeneration-related protein 2- and Purkinje cell antibody 2-associated ACA, discusses differential diagnostic aspects and provides a summary and outlook.
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medusa head ataxia the expanding spectrum of purkinje cell antibodies in autoimmune cerebellar ataxia part 3 anti yo cdr2 anti nb ap3b2 pca 2 anti tr dner other antibodies diagnostic pitfalls summary and outlook
Journal of Neuroinflammation, 2015Co-Authors: S. Jarius, B. WildemannAbstract:Serological testing for anti-neural autoantibodies is important in patients presenting with idiopathic cerebellar ataxia, since these autoantibodies may indicate cancer, determine treatment and predict prognosis. While some of them target nuclear antigens present in all or most CNS neurons (e.g. anti-Hu, anti-Ri), others more specifically target antigens present in the cytoplasm or plasma membrane of Purkinje cells (PC). In this series of articles, we provide a detailed review of the clinical and paraclinical features, oncological, therapeutic and prognostic implications, pathogenetic relevance, and differential laboratory diagnosis of the 12 most common PC autoantibodies (often referred to as ‘Medusa head antibodies’ due to their characteristic somatodendritic binding pattern when tested by immunohistochemistry). To assist immunologists and neurologists in diagnosing these disorders, typical high-resolution immunohistochemical images of all 12 reactivities are presented, diagnostic pitfalls discussed and all currently available assays reviewed. Of note, most of these antibodies target antigens involved in the mGluR1/calcium pathway essential for PC function and survival. Many of the antigens also play a role in spinocerebellar ataxia. Part 1 focuses on anti-metabotropic glutamate receptor 1-, anti-Homer protein homolog 3-, anti-Sj/inositol 1,4,5-trisphosphate receptor- and anti-carbonic anhydrase-related protein VIII-associated autoimmune cerebellar ataxia (ACA); part 2 covers anti-protein kinase C gamma-, anti-glutamate receptor delta-2-, anti-Ca/RhoGTPase-activating protein 26- and anti-voltage-gated calcium channel-associated ACA; and part 3 reviews the current knowledge on anti-Tr/delta notch-like epidermal growth factor-related receptor-, anti-Nb/AP3B2-, anti-Yo/cerebellar degeneration-related protein 2- and Purkinje cell antibody 2-associated ACA, discusses differential diagnostic aspects and provides a summary and outlook.
Renwei Jing - One of the best experts on this subject based on the ideXlab platform.
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the mutation of the AP3B1 gene causes uterine hypoplasia in pearl mice
Reproductive Sciences, 2020Co-Authors: Renwei Jing, Haiqing Zhang, Yu Kong, Xuan Dong, Jie Yan, Jia Han, Gang Han, Jingye Zhang, Lijun FengAbstract:The pearl (pe) mouse mutant has been identified as a model for Hermansky-Pudlak syndrome and bears a mutation in the beta3A subunit of the AP-3 complex, which has a core function in the biogenesis and function of various lysosomal-related organelles. Through large-scale mating, we found that female pearl mice also displayed reduced fertility with a smaller litter size. Abnormal uteri in both 1-month-old and 3-month-old mice were observed as having short and thin uterine horns, indicating abnormal development. Histological studies revealed that the endometrial epithelium and endometrial stoma of the uterus were both thinner than those in the normal controls. We examined some key factors in uterine development, including the Hoxa10, Hoxa11, and Wnt5a genes, and found that they all presented lower mRNA and protein levels. The pearl mouse could serve as a model for uterine hypoplasia, a common problem in female infertility.
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correction to the mutation of the AP3B1 gene causes uterine hypoplasia in pearl mice
Reproductive Sciences, 2020Co-Authors: Renwei Jing, Haiqing Zhang, Yu Kong, Xuan Dong, Jie Yan, Gang Han, Jingye Zhang, Jia HanAbstract:The authors are deeply sorry that, due to an unintentional mistake, the proof-editing procedure was skipped. A major mistake must be corrected: Fig. 2C contains pictures from a mislabeled folder and should be replaced as shown in the updated Fig. 2 below.
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Different functions of biogenesis of lysosomal organelles complex 3 subunit 1 (Hps1) and adaptor-related protein complex 3, beta 1 subunit (AP3B1) genes on spermatogenesis and male fertility.
Reproduction fertility and development, 2019Co-Authors: Renwei Jing, Haiqing Zhang, Yu Kong, Xuan Dong, Jie Yan, Jia Han, Lijun FengAbstract:Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder in humans and mice. Pale ear (ep) and pearl (pe) mice, bearing mutations in the biogenesis of lysosomal organelles complex 3 subunit 1 (Hps1) and adaptor-related protein complex 3, beta 1 subunit (AP3B1) genes respectively, are mouse models of human HPS Type 1 (HPS1) and Type 2 (HPS2) respectively. In the present study we investigated and compared the reduced fertilities of ep and pe male mice. Both ep and pe males exhibited lower abilities to impregnate C57BL/6J (B6) females, and B6 females mated with ep males produced smaller litters than those mated with pe males. Delayed testis development, reduced sperm count and lower testosterone concentrations were observed in the pe but not ep male mice. However, the reduction in sperm motility was greater in ep than pe males, likely due to the mitochondrial and fibrous sheath abnormalities observed by electron microscopy in the sperm tails of ep males. Together, the results indicate that the Hps1 and AP3B1 genes play distinct roles in male reproductive system development and spermatogenesis in mice, even though ep and pe males share common phenotypes, including reduced lysosomes in Sertoli cells and dislocated Zn2+ in sperm heads.
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The AP3B1 gene regulates the ocular melanosome biogenesis and tyrosinase distribution differently from the Hps1 gene
Experimental eye research, 2014Co-Authors: Renwei Jing, Xuan Dong, Jie Yan, Xiangyuan Chen, Lijun FengAbstract:Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder in humans and mice. The pearl (pe) mouse, a mouse model for the human HPS-2, bears a mutation in AP3B1 gene. Here we investigated the pigmentation in eyes of pearl (pe) mice, and compared it with our previously published data in pale ear (ep) mice. We revealed that the hypopigmentation in eyes of pearl mice was more severe than pale ear mice, especially in the neural crest-derived tissues. However, the total tyrosinase activity in eyes of pearl mice was stronger than pale ear mice, suggesting that the degradation of aberrantly transported tyrosinase in eyes of pearl mice was weaker than that of pale ear mice. Furthermore, the pigmentation in eyes of mice doubly heterozygous for Hps1 and AP3B1 genes was similar to the wild-type, while the hypopigmentation in iris of double mutant mice was more severe than either single mutant. Besides, we found several previously reported characters in pale ear mice, including macromelanosomes in the neural crest-derived melanocytes and increased accumulation of lipofuscin in the RPE, were absent in pearl mice. Our study indicates that AP3B1 gene play distinct roles in melanin production and tyrosinase distribution compared with Hps1 gene.
Yu Kong - One of the best experts on this subject based on the ideXlab platform.
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correction to the mutation of the AP3B1 gene causes uterine hypoplasia in pearl mice
Reproductive Sciences, 2020Co-Authors: Renwei Jing, Haiqing Zhang, Yu Kong, Xuan Dong, Jie Yan, Gang Han, Jingye Zhang, Jia HanAbstract:The authors are deeply sorry that, due to an unintentional mistake, the proof-editing procedure was skipped. A major mistake must be corrected: Fig. 2C contains pictures from a mislabeled folder and should be replaced as shown in the updated Fig. 2 below.
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the mutation of the AP3B1 gene causes uterine hypoplasia in pearl mice
Reproductive Sciences, 2020Co-Authors: Renwei Jing, Haiqing Zhang, Yu Kong, Xuan Dong, Jie Yan, Jia Han, Gang Han, Jingye Zhang, Lijun FengAbstract:The pearl (pe) mouse mutant has been identified as a model for Hermansky-Pudlak syndrome and bears a mutation in the beta3A subunit of the AP-3 complex, which has a core function in the biogenesis and function of various lysosomal-related organelles. Through large-scale mating, we found that female pearl mice also displayed reduced fertility with a smaller litter size. Abnormal uteri in both 1-month-old and 3-month-old mice were observed as having short and thin uterine horns, indicating abnormal development. Histological studies revealed that the endometrial epithelium and endometrial stoma of the uterus were both thinner than those in the normal controls. We examined some key factors in uterine development, including the Hoxa10, Hoxa11, and Wnt5a genes, and found that they all presented lower mRNA and protein levels. The pearl mouse could serve as a model for uterine hypoplasia, a common problem in female infertility.
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Different functions of biogenesis of lysosomal organelles complex 3 subunit 1 (Hps1) and adaptor-related protein complex 3, beta 1 subunit (AP3B1) genes on spermatogenesis and male fertility.
Reproduction fertility and development, 2019Co-Authors: Renwei Jing, Haiqing Zhang, Yu Kong, Xuan Dong, Jie Yan, Jia Han, Lijun FengAbstract:Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder in humans and mice. Pale ear (ep) and pearl (pe) mice, bearing mutations in the biogenesis of lysosomal organelles complex 3 subunit 1 (Hps1) and adaptor-related protein complex 3, beta 1 subunit (AP3B1) genes respectively, are mouse models of human HPS Type 1 (HPS1) and Type 2 (HPS2) respectively. In the present study we investigated and compared the reduced fertilities of ep and pe male mice. Both ep and pe males exhibited lower abilities to impregnate C57BL/6J (B6) females, and B6 females mated with ep males produced smaller litters than those mated with pe males. Delayed testis development, reduced sperm count and lower testosterone concentrations were observed in the pe but not ep male mice. However, the reduction in sperm motility was greater in ep than pe males, likely due to the mitochondrial and fibrous sheath abnormalities observed by electron microscopy in the sperm tails of ep males. Together, the results indicate that the Hps1 and AP3B1 genes play distinct roles in male reproductive system development and spermatogenesis in mice, even though ep and pe males share common phenotypes, including reduced lysosomes in Sertoli cells and dislocated Zn2+ in sperm heads.