Loss of a homologous group of proteins in a dominantly inherited ectodermal malformation

Abstract

Hair from mice bearing the dominantly inherited Naked trait (NN) and from normal (NN) mice of the same inbred strain was separated into its major protein components by standard techniques. The relative amounts of proteins in these components were then determined by a regression method from the amino acid composition of the hair samples and of the fractions into which they had been separated. The results indicated that the amount of soluble fibril in Naked-mouse hair is decreased. Polyacrylamide-gel electrophoresis of this fraction prepared from the hair of both normal and Naked mice revealed that all protein bands present in the normal are also present in the Naked mice. However, a densitometric scan of the gels at 280 nm showed that the soluble fibril fraction from Naked-mouse hair is deficient in several proteins which, on amino acid analysis, were found to contain 31% glycine and 10% tyrosine. Gel filtration of S-carboxymethylkerateine prepared from normal and mutant hair showed that the mutant hair is deficient in a heterogeneous, low-molecular-weight fraction also rich in glycine and tyrosine. Our present data do not reveal the mechanism whereby a single gene locus modulates the production of several different proteins.

Protein and amino acid composition of hair from mice carrying the naked (N) gene

“…This paper describes the results of electrophoretic analysis of HS, HT and LS proteins from + / +, N/ + and N/N hair, and the results of amino acid analysis of the three hair types. Our results confirm the findings of Tenenhouse & Gold (1976), and from the analysis of N/N hair we conclude that the N gene exerts its effects on the synthesis of hair proteins via some indirect route.…”

“…Moreover the degree to which the HT protein content was reduced was similar in the two studies, for Tenenhouse & Gold (1976) estimated that the HT protein contents + / + and N/ + hair were 16 and 8 % respectively, while our estimates of the average amount of HT protein contents in the two hair types were 13 and 8% respectively.…”

“…Some of the spots may have contained more than one component, for Gillespie (1972) found about 20 HT proteins in mouse hair using starch gel electrophoresis and Tenenhouse & Gold (1976) found 12 HT proteins using polyacrylamide gel electrophoresis. In our gels HT 2, HT 4, HT 6 and HT 7 were the most intense spots, HT 1, HT 3 and HT 5 were less intense and HT 8 was very faint.…”

“…This cortical protein consists of microfibrils, composed essentially of low-sulphur (LS) proteins, embedded in a matrix of high-sulphur (HS) and high-tyrosine (HT) proteins (Fraser, Macrae & Rogers, 1972). Tenenhouse & Gold (1976) and Marshall, Frenkel & Gillespie (1977), who compared the HS and HT proteins extracted from + / + and N/ + hair, were unable to find qualitative differences between the two genotypes but + / + hair was found to contain twice as much HT proteins as N/ + hair (Tenenhouse & Gold, 1976). Hair from + / + mice was also found to contain more tyrosine and glycine than N/ + hair (Tenenhouse et al 1974); both amino acids are known to be present in comparatively large amounts in HT proteins.…”

“…Biochemical analyses (Tenenhouse et al 1974;Tenenhouse & Gold, 1976) of N/ + hair showed that it is unlikely that the N gene codes for a specific HT or HS protein but that it may act by affecting the production of the whole family of HT proteins. However in order to decide more conclusively between the possible influences of the N gene, it is necessary to examine hair from N/N mice.…”