{"id":{"repo_id":"freiburg-diss","oai_identifier":"oai:freidok.uni-freiburg.de:724"},"canonical_url":"https://search.dev.ndltd.org/etd/freiburg-diss/oai:freidok.uni-freiburg.de:724","repository":{"repo_id":"freiburg-diss","name":"University of Freiburg","base_url":"https://freidok.uni-freiburg.de/oai/oai2.php"},"display":{"title":"Biochemical and genetic analysis of the adaptor protein SH3P7 : insights from a newly generated knockout mouse","abstract":"SH3P7 (mAbp1/Hip55) is a widely expressed actin-binding adaptor protein identified as a substrate for protein tyrosine kinase (PTK) after BCR activation. In addition to two protein-binding modules specific for filamentous actin, SH3P7 also contains an SH3 domain. The biochemical studies presented here, show that SH3P7 interacts via this domain with key components of endocytosis in B cells. SH3P7 binding to Hip1R, a huntingtin family member and new component of clathrin-coated vesicles, is characterized in greater detail. In resting B cells, Hip1R is constitutively bound to SH3P7. Stimulation of B cells with BCR-crosslinking-antibody or pervanadate-treatment, abolishes the interaction in a time-dependent manner. Thus the SH3P7/Hip1R interaction might be a structural link between BCR activation, the actin-cytoskeleton and endocytosis. To inactivate the mouse sh3p7 gene, the gene was first cloned and characterized. This allowed the construction of a deletion vector, which was used to target the sh3p7 gene in embryonic stem cells. Sh3p7-/- mice were successfully produced and are viable and fertile. Initial experiments with sh3p7-/- B cells indicate a role of SH3P7 as inhibitor of BCR internalization. Male sh3p7-/- and sh3p7+/- mice of this strain develop splenomegaly and a progressive and ultimately fatal disease at 3-4 months of age. Initial FACS-analysis of the cellular composition of the spleen show drastic reduction of T1 B cells which might be interpreted as defect in B cell development or maturation. Symptoms such as progressive paralysis implicate a neuronal disease in male sh3p7-/- and sh3p7+/- mice. Future detailed studies of the sh3p7 knockout might give insight into related human diseases. <br>In summary provides this work evidence for a function of SH3P7 in BCR endocytosis and shows the result of the generation and initial analysis of a new knockout mouse.","abstract_html":"SH3P7 (mAbp1/Hip55) is a widely expressed actin-binding adaptor protein identified as a substrate for protein tyrosine kinase (PTK) after BCR activation. In addition to two protein-binding modules specific for filamentous actin, SH3P7 also contains an SH3 domain. The biochemical studies presented here, show that SH3P7 interacts via this domain with key components of endocytosis in B cells. SH3P7 binding to Hip1R, a huntingtin family member and new component of clathrin-coated vesicles, is characterized in greater detail. In resting B cells, Hip1R is constitutively bound to SH3P7. Stimulation of B cells with BCR-crosslinking-antibody or pervanadate-treatment, abolishes the interaction in a time-dependent manner. Thus the SH3P7/Hip1R interaction might be a structural link between BCR activation, the actin-cytoskeleton and endocytosis. To inactivate the mouse sh3p7 gene, the gene was first cloned and characterized. This allowed the construction of a deletion vector, which was used to target the sh3p7 gene in embryonic stem cells. Sh3p7-/- mice were successfully produced and are viable and fertile. Initial experiments with sh3p7-/- B cells indicate a role of SH3P7 as inhibitor of BCR internalization. Male sh3p7-/- and sh3p7+/- mice of this strain develop splenomegaly and a progressive and ultimately fatal disease at 3-4 months of age. Initial FACS-analysis of the cellular composition of the spleen show drastic reduction of T1 B cells which might be interpreted as defect in B cell development or maturation. Symptoms such as progressive paralysis implicate a neuronal disease in male sh3p7-/- and sh3p7+/- mice. Future detailed studies of the sh3p7 knockout might give insight into related human diseases. &lt;br&gt;In summary provides this work evidence for a function of SH3P7 in BCR endocytosis and shows the result of the generation and initial analysis of a new knockout mouse.","abstract_has_math":false,"creators":["Connert, Sabine"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Reth, Michael"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-24T02:21:52Z","subjects":["SH3P7","Hip1R","Clathrin-vermittelte Endocytose","BCR Internalisierung","BCR internalisation","clathrin-mediated endocytosis"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://freidok.uni-freiburg.de/data/724","outbound_label":"Repository record","outbound_source":"source_url"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Reth, Michael"]},{"key":"dc:creator","label":"Author","values":["Connert, Sabine"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:type","label":"Dc Type","values":["DoctoralThesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["SH3P7","Hip1R","Clathrin-vermittelte Endocytose","BCR Internalisierung","BCR internalisation","clathrin-mediated endocytosis"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["SH3P7 (mAbp1/Hip55) is a widely expressed actin-binding adaptor protein identified as a substrate for protein tyrosine kinase (PTK) after BCR activation. In addition to two protein-binding modules specific for filamentous actin, SH3P7 also contains an SH3 domain. The biochemical studies presented here, show that SH3P7 interacts via this domain with key components of endocytosis in B cells. SH3P7 binding to Hip1R, a huntingtin family member and new component of clathrin-coated vesicles, is characterized in greater detail. In resting B cells, Hip1R is constitutively bound to SH3P7. Stimulation of B cells with BCR-crosslinking-antibody or pervanadate-treatment, abolishes the interaction in a time-dependent manner. Thus the SH3P7/Hip1R interaction might be a structural link between BCR activation, the actin-cytoskeleton and endocytosis. To inactivate the mouse sh3p7 gene, the gene was first cloned and characterized. This allowed the construction of a deletion vector, which was used to target the sh3p7 gene in embryonic stem cells. Sh3p7-/- mice were successfully produced and are viable and fertile. Initial experiments with sh3p7-/- B cells indicate a role of SH3P7 as inhibitor of BCR internalization. Male sh3p7-/- and sh3p7+/- mice of this strain develop splenomegaly and a progressive and ultimately fatal disease at 3-4 months of age. Initial FACS-analysis of the cellular composition of the spleen show drastic reduction of T1 B cells which might be interpreted as defect in B cell development or maturation. Symptoms such as progressive paralysis implicate a neuronal disease in male sh3p7-/- and sh3p7+/- mice. Future detailed studies of the sh3p7 knockout might give insight into related human diseases. <br>In summary provides this work evidence for a function of SH3P7 in BCR endocytosis and shows the result of the generation and initial analysis of a new knockout mouse."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Biochemical and genetic analysis of the adaptor protein SH3P7 : insights from a newly generated knockout mouse","Biochemische und genetische Studien des Adaptorproteins SH3P7 : Einsichten durch eine neu generierte Knockout Maus"]}]}],"canonical_facts":{"dc:contributor":["Reth, Michael"],"dc:creator":["Connert, Sabine"],"dc:description.abstract":["SH3P7 (mAbp1/Hip55) is a widely expressed actin-binding adaptor protein identified as a substrate for protein tyrosine kinase (PTK) after BCR activation. In addition to two protein-binding modules specific for filamentous actin, SH3P7 also contains an SH3 domain. The biochemical studies presented here, show that SH3P7 interacts via this domain with key components of endocytosis in B cells. SH3P7 binding to Hip1R, a huntingtin family member and new component of clathrin-coated vesicles, is characterized in greater detail. In resting B cells, Hip1R is constitutively bound to SH3P7. Stimulation of B cells with BCR-crosslinking-antibody or pervanadate-treatment, abolishes the interaction in a time-dependent manner. Thus the SH3P7/Hip1R interaction might be a structural link between BCR activation, the actin-cytoskeleton and endocytosis. To inactivate the mouse sh3p7 gene, the gene was first cloned and characterized. This allowed the construction of a deletion vector, which was used to target the sh3p7 gene in embryonic stem cells. Sh3p7-/- mice were successfully produced and are viable and fertile. Initial experiments with sh3p7-/- B cells indicate a role of SH3P7 as inhibitor of BCR internalization. Male sh3p7-/- and sh3p7+/- mice of this strain develop splenomegaly and a progressive and ultimately fatal disease at 3-4 months of age. Initial FACS-analysis of the cellular composition of the spleen show drastic reduction of T1 B cells which might be interpreted as defect in B cell development or maturation. Symptoms such as progressive paralysis implicate a neuronal disease in male sh3p7-/- and sh3p7+/- mice. Future detailed studies of the sh3p7 knockout might give insight into related human diseases. <br>In summary provides this work evidence for a function of SH3P7 in BCR endocytosis and shows the result of the generation and initial analysis of a new knockout mouse."],"dc:format.medium":["application/pdf"],"dc:subject":["SH3P7","Hip1R","Clathrin-vermittelte Endocytose","BCR Internalisierung","BCR internalisation","clathrin-mediated endocytosis"],"dc:title":["Biochemical and genetic analysis of the adaptor protein SH3P7 : insights from a newly generated knockout mouse","Biochemische und genetische Studien des Adaptorproteins SH3P7 : Einsichten durch eine neu generierte Knockout Maus"],"dc:type":["DoctoralThesis"]},"updated_at":"2026-07-24T02:21:52Z"}