Hereditary Nephritis 
A defect in glomerular basement membrane 
(GBM), one of the major components of the renal 
filtration mechanism, is responsible for the progres- 
sive deterioration in kidney function in hereditary 
nephritis (Alport syndrome) . The common form of 
this disease is caused by a mutation in the a5 chain 
of type IV collagen. Dr. Reeders and his colleagues 
have identified a second form of the disease charac- 
terized by autosomal recessive inheritance. In addi- 
tion, members of the laboratory have cloned tw^o 
novel type IV collagen chains, a5{TV) and a4(IV), 
w^hich are frequently absent from the basement 
membranes of patients w^ith Alport syndrome. These 
genes, which have been mapped to human chromo- 
some 2, are linked to the recessive form of the dis- 
ease, suggesting that mutation of one or both of 
these genes in a homozygous state also causes hered- 
itary nephritis. Dr. Mariko Mariyama has shown that 
the q:3(IV) and a4(YV) chains are arranged in a 
head-to-head fashion and has isolated the genes on a 
yeast artificial chromosome so that further character- 
ization of the mutations can be expedited. 
The a3(lV) chain is also the target for autoanti- 
bodies in Goodpasture syndrome, a rare disorder in 
which autoimmune destruction of glomerular and 
pulmonary basement membranes is observed. In col- 
laboration with Dr. Billy Hudson (University of Kan- 
sas), the B cell epitope has been localized within 
the noncollagenous domain of the a3(IV) chain. 
Further work on the expression of the chain and 
derivative mutants will permit characterization of 
the immune reaction in this disease. 
Dr. Reeders is also Associate Professor of Inter- 
nal Medicine and of Genetics at Yale University 
School of Medicine. 
Books and Chapters of Books 
Reeders, S.T. 1992. Genetic abnormalities of renal 
function. In The Kidney: Physiology and Patho- 
physiology (Seldin, D.W., and Giebisch, G, Eds.). 
New York: Raven, pp 3085-3 HI. 
Reeders, S.T. 1992. Molecular genetics of renal 
disorders. In Oxford Textbook of Clinical Ne- 
phrology (Cameron, S., Davison, A.M., Griinfeld, 
J.P., Kerr, D., and Ritz, E., Eds ). New York: Ox- 
ford University Press, pp 2155-2163. 
Articles 
Ceccherini, I., Romeo, G., Lawrence, S., Breuning, 
M.H., Harris, P.C., Himmelbauer, H., Frischauf, 
A.M., Sutherland, G.R., Germino, G.G., Reeders, 
S.T., and Morton, N.E. 1992. Construction of a 
map of chromosome 16 by using radiation hy- 
brids. Proc Natl Acad Sci USA 89:104-108. 
Dudley, C.R.K., Giuffra, L.A., Raine, A.E.G., and 
Reeders, S.T. 1991. Assessing the role of APNH, a 
gene encoding for a human amiloride-sensitive 
Na^/H^ antiporter, on the interindividual varia- 
tion in red cell Na^/Li^ countertransport. / Am 
Soc Nephrol 2:937-943. 
Germino, G.G., Weinstat-Saslow, D., Himmelbauer, 
H., Gillespie, G.A.J. , Somlo, S., Wirth, B., Barton, 
N., Harris, K.L., Frischauf, A.-M., and Reeders, 
S.T. 1992. The gene for autosomal dominant 
polycystic kidney disease lies in a 750-kb CpG- 
rich region. Genomics 13:144-151. 
Himmelbauer, H., Pohlschmidt, M., Snarey, A., Ger- 
mino, G.G., Weinstat-Saslow, D., Somlo, S., 
Reeders, S.T., and Frischauf, A.M. 1992. Human- 
mouse homologies in the region of the polycystic 
kidney disease gene (PKDl). Genomics 13:35-38. 
IJdo, J.W., Baldini, A., Ward, DC, Reeders, S.T., 
and Wells, R.A. 1991 • Origin of human chromo- 
some 2: an ancestral telomere-telomere fusion. 
Proc Natl Acad Sci USA 88:905 1-9055. 
IJdo, J.W., Baldini, A., Wells, R.A., Ward, DC, and 
Reeders, S.T. 1992. FRA2B is distinct from in- 
verted telomere repeat arrays at 2ql3. Genomics 
12:833-835. 
IJdo, J.W., Wells, R.A., Baldini, A., and Reeders, 
S.T. 1991- Improved telomere detection using a 
telomere repeat probe (TTAGGG)n generated by 
PCR. Nucleic Acids Res 19:4780. 
Kalluri, R., Gunwar, S., Reeders, S.T., Morrison, 
K.C., Mariyama, M., Ebner, K.E., Noelken, M.E., 
and Hudson, B.G. 1991. Goodpasture syndrome. 
Localization of the epitope for the autoantibodies 
to the carboxyl-terminal region of the a3(IV) 
chain of basement membrane collagen. / Biol 
Chem 266:24018-24024. 
Mariyama, M., Kalluri, R., Hudson, B.G., and 
Reeders, S.T. 1992. The a4(IV) chain of base- 
ment membrane collagen. Isolation of cDNAs en- 
coding bovine aA(W) and comparison with other 
type IV coUagens./S/o/ Chem 267:1253-1258. 
Mariyama, M., Zheng, K.G., Yang-Feng, T.L., and 
Reeders, S.T. 1992. Colocalization of the genes 
for the a3(IV) and a4(IV) chains of type IV colla- 
gen to chromosome 2 bands q35-q37. Genomics 
13:809-813. 
Morrison, K.E., Mariyama, M., Yang-Feng, T.L., and 
Reeders, S.T. 1991. Sequence and localization of 
a partial cDNA encoding the human a-3 chain of 
type IV collagen. Am f Hum Genet 49:545-554. 
Reeders, S.T. 1992. Genetic heterogeneity and 
clinical disease [editorial]. West J Med 156:555- 
556. 
GENETICS 253 
