# STUDY OF RENAL DISEASES IN CHILDHOOD

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 1988 · $267,312

## Abstract

The objective is to study and resolve the riddles of certain diseases in
childhood, specifically those associated with abnormalities of the
glomerular capillary filter.  The grant focuses on research that will help
us understand the pathogenesis of familial forms of renal disease including
Alport-type familial nephritis, nephrotic syndrome, and glomerulonephritis.

This proposal is predicated on observations that an antigenic
determinant(s) on the non-collagenous domain (NC1) of type IV collagen is
not detected on the glomerular basement (GBM) membrane and epidermal
basement membrane (EBM) of males with Alport-type familial nephritis
whereas in affected females the EBM shows zones of reactivity separated by
gaps of non-reactivity, supporting X-linked dominant inheritance.  Direct
analysis of Alport kidney basement membrane by PAGE and 2-dimensional gel
analysis demonstrates absence of a normally-occurring 28 kDa antigenic
component.  Studies include further antigenic analysis of affected
kindreds; development of highly specific and informative monoclonal
antibodies; detailed analyses of NC1 monomers and dimers; and development
of cDNA probes to the NC1 component.

The proposal is concerned with components of the human glomerular visceral
epithelium and basement membrane.  We will characterize the role of a
previously unrecognized component of human GBM - MBM15 antigen - which
appears early in ontogeny, is a component of epithelial spikes in
membranous nephropathy; is synthesized by human glomerular epithelial cells
in culture, and is a normal urinary constituent.  Studies will be carried
out on human glomerular polyanion (GPA) (podocalyxin), a negatively-charged
sialoprotein that covers the surface of viscerel eplithelial cells, and
proteoglycan located in the lamina rara of the GBM--in order to define
further their role in human disease.  We have shown that human glomerular
epithelium in culture synthesize a variety of components including
proteoglycans, MBM15 antigen, collagen IV, laminin, fibronectin, and
certain lymphohemopoietic antigens.  The role of the epithelial cell in
modulating and controlling components of the glomerular capillary will be
addressed.

The methods used include cell culture, immunohistochemistry, morphology,
biochemistry, immunology, and cDNA technology.

## Key facts

- **NIH application ID:** 3124771
- **Project number:** 5R01AI010704-28
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **SAM.gov UEI:** KABJZBBJ4B54
- **Principal Investigator:** ALFRED F MICHAEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $267,312
- **Award type:** 5
- **Project period:** 1976-12-01 → 1991-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124771

## Citation

> US National Institutes of Health, RePORTER application 3124771, STUDY OF RENAL DISEASES IN CHILDHOOD (5R01AI010704-28). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124771. Licensed CC0.

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