Minimal Kidney Disease Phenotype in Heterozygous Null Mice
Background: Shroom family member 3 (SHROOM3) encodes an actin-associated protein that regulates epithelial morphology during development. Several genome-wide association studies (GWAS) have identified genetic variances primarily in the 5’ region of SHROOM3, associated with chronic kidney disease (CK...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2023-06-01
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| Series: | Canadian Journal of Kidney Health and Disease |
| Online Access: | https://doi.org/10.1177/20543581231165716 |
| _version_ | 1797808874914316288 |
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| author | Allison Lawlor Kristina Cunanan Joanna Cunanan Amy Paul Hadiseh Khalili Doyun Ko Ahsan Khan Robert Gros Thomas Drysdale Darren Bridgewater |
| author_facet | Allison Lawlor Kristina Cunanan Joanna Cunanan Amy Paul Hadiseh Khalili Doyun Ko Ahsan Khan Robert Gros Thomas Drysdale Darren Bridgewater |
| author_sort | Allison Lawlor |
| collection | DOAJ |
| description | Background: Shroom family member 3 (SHROOM3) encodes an actin-associated protein that regulates epithelial morphology during development. Several genome-wide association studies (GWAS) have identified genetic variances primarily in the 5’ region of SHROOM3, associated with chronic kidney disease (CKD) and poor transplant outcomes. These genetic variants are associated with alterations in Shroom3 expression. Objective: Characterize the phenotypic abnormalities associated with reduced Shroom3 expression in postnatal day 3-, 1-month and 3-month-old mice. Methods: The Shroom3 protein expression pattern was determined by immunofluorescence. We generated Shroom3 heterozygous null mice ( Shroom3 Gt/+ ) and performed comparative analyses with wild type littermates based on somatic and kidney growth, gross renal anatomy, renal histology, renal function at postnatal day 3, 1 month, and 3 months. Results: The Shroom3 protein expression localized to the apical regions of medullary and cortical tubular epithelium in postnatal wild type kidneys. Co-immunofluorescence studies confirmed protein expression localized to the apical side of the tubular epithelium in proximal convoluted tubules, distal convoluted tubules, and collecting ducts. While Shroom3 heterozygous null mice exhibited reduced Shroom3 protein expression, no differences in somatic and kidney growth were observed when compared to wild type mice. Although, rare cases of unilateral hypoplasia of the right kidney were observed at postnatal 1 month in Shroom3 heterozygotes. Yet renal histological analysis did not reveal any overt abnormalities in overall kidney structure or in glomerular and tubular organization in Shroom3 heterozygous null mice when compared to wild type mice. Analysis of the apical-basolateral orientation of the tubule epithelium demonstrated alterations in the proximal convoluted tubules and modest disorganization in the distal convoluted tubules at 3 months in Shroom3 heterozygotes. Additionally, these modest abnormalities were not accompanied by tubular injury or physiological defects in renal and cardiovascular function. Conclusion: Taken together, our results describe a mild kidney disease phenotype in adult Shroom3 heterozygous null mice, suggesting that Shroom3 expression and function may be required for proper structure and maintenance of the various tubular epithelial parenchyma of the kidney. |
| first_indexed | 2024-03-13T06:44:10Z |
| format | Article |
| id | doaj.art-4f3aee176f314473832c15187a140149 |
| institution | Directory Open Access Journal |
| issn | 2054-3581 |
| language | English |
| last_indexed | 2024-03-13T06:44:10Z |
| publishDate | 2023-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Canadian Journal of Kidney Health and Disease |
| spelling | doaj.art-4f3aee176f314473832c15187a1401492023-06-08T08:33:20ZengSAGE PublishingCanadian Journal of Kidney Health and Disease2054-35812023-06-011010.1177/20543581231165716Minimal Kidney Disease Phenotype in Heterozygous Null MiceAllison Lawlor0Kristina Cunanan1Joanna Cunanan2Amy Paul3Hadiseh Khalili4Doyun Ko5Ahsan Khan6Robert Gros7Thomas Drysdale8Darren Bridgewater9Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, CanadaDepartment of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, CanadaToronto General Hospital Research Institute, University Health Network, Ontario, CanadaDepartment of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, CanadaToronto General Hospital Research Institute, University Health Network, Ontario, CanadaDepartment of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, Ontario, CanadaDepartment of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, CanadaDepartment of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, Ontario, CanadaDepartment of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, Ontario, CanadaDepartment of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, CanadaBackground: Shroom family member 3 (SHROOM3) encodes an actin-associated protein that regulates epithelial morphology during development. Several genome-wide association studies (GWAS) have identified genetic variances primarily in the 5’ region of SHROOM3, associated with chronic kidney disease (CKD) and poor transplant outcomes. These genetic variants are associated with alterations in Shroom3 expression. Objective: Characterize the phenotypic abnormalities associated with reduced Shroom3 expression in postnatal day 3-, 1-month and 3-month-old mice. Methods: The Shroom3 protein expression pattern was determined by immunofluorescence. We generated Shroom3 heterozygous null mice ( Shroom3 Gt/+ ) and performed comparative analyses with wild type littermates based on somatic and kidney growth, gross renal anatomy, renal histology, renal function at postnatal day 3, 1 month, and 3 months. Results: The Shroom3 protein expression localized to the apical regions of medullary and cortical tubular epithelium in postnatal wild type kidneys. Co-immunofluorescence studies confirmed protein expression localized to the apical side of the tubular epithelium in proximal convoluted tubules, distal convoluted tubules, and collecting ducts. While Shroom3 heterozygous null mice exhibited reduced Shroom3 protein expression, no differences in somatic and kidney growth were observed when compared to wild type mice. Although, rare cases of unilateral hypoplasia of the right kidney were observed at postnatal 1 month in Shroom3 heterozygotes. Yet renal histological analysis did not reveal any overt abnormalities in overall kidney structure or in glomerular and tubular organization in Shroom3 heterozygous null mice when compared to wild type mice. Analysis of the apical-basolateral orientation of the tubule epithelium demonstrated alterations in the proximal convoluted tubules and modest disorganization in the distal convoluted tubules at 3 months in Shroom3 heterozygotes. Additionally, these modest abnormalities were not accompanied by tubular injury or physiological defects in renal and cardiovascular function. Conclusion: Taken together, our results describe a mild kidney disease phenotype in adult Shroom3 heterozygous null mice, suggesting that Shroom3 expression and function may be required for proper structure and maintenance of the various tubular epithelial parenchyma of the kidney.https://doi.org/10.1177/20543581231165716 |
| spellingShingle | Allison Lawlor Kristina Cunanan Joanna Cunanan Amy Paul Hadiseh Khalili Doyun Ko Ahsan Khan Robert Gros Thomas Drysdale Darren Bridgewater Minimal Kidney Disease Phenotype in Heterozygous Null Mice Canadian Journal of Kidney Health and Disease |
| title | Minimal Kidney Disease Phenotype in Heterozygous Null Mice |
| title_full | Minimal Kidney Disease Phenotype in Heterozygous Null Mice |
| title_fullStr | Minimal Kidney Disease Phenotype in Heterozygous Null Mice |
| title_full_unstemmed | Minimal Kidney Disease Phenotype in Heterozygous Null Mice |
| title_short | Minimal Kidney Disease Phenotype in Heterozygous Null Mice |
| title_sort | minimal kidney disease phenotype in heterozygous null mice |
| url | https://doi.org/10.1177/20543581231165716 |
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