Summary. Hereditary syndromes with congenital deafness and hypothyroidism have been reported from many countries. The large majority of them are believed to form a single genetic entity, known as Pendred's syndrome, and inherited as a recessive trait. The anatomical basis of deafness is not known. It is generally believed that deafness and hypothyroidism are not causally related, but are independent effects of the gene. The object of this investigation was to test this view by means ofinduced hypothyroidism. Mice from the inbred strain C57BL/Gr were given 0-1% propylthiouracil (PTU) in drinking water, and their offspring were examined. They were found to be practically deaf, and to have serious abnormalities in the inner ear. Addition of thyroxine to the drinking water containing PTU resulted in normal hearing and a normal inner ear, showing that the abnormalities were not caused by PTU as such, but were the consequence ofits inhibitory effect on thyroid function. It is, therefore, highly probable that in Pendred's syndrome and other similar conditions the loss of hearing is secondary to hypothyroidism during fetal life. Suggestions are put forward for mitigating the expressions of these syndromes by treatment with thyroxine during certain stages of development.Hereditary deafness associated with hypothyroidism has been observed in a large number of families in many countries (full references in Fraser, 1965;McKusick, 1971). As the clinical features vary a good deal, it is not possible to say how many distinct genetic entities are involved, but the large majority of these families are similar enough to be regarded as having the same syndrome. Fraser, Morgans, and Trotter (1960) have named it Pendred's syndrome, after Vaughan Pendred who first described it in 1896. Fraser (1965) has shown that it is inherited as a recessive trait, although some minor effects of the gene may be detectable in the heterozygote. He gives the frequency of affected persons in the British Isles as 0 000,075, frequency of the mutant gene causing it as 0-008, and the mutation rate as 56 per million loci per generation. Batsakis and Nishiyama (1962) have estimated that this syndrome accounts for 1 to 10%' of all hereditary deafness.

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Two years ago Deol (1956) reported the first case of inherited deafness in the mouse not associated with any of the usual concomitant locomotor disturbances. It was followed by a systematic search of the mouse colony of this laboratory, which resulted in the discovery of several other cases of the same kind. The mutant gene described here is one of them. The name deafness, symbol dn, is proposed for it. HEARING ABILITY AND BEHAVIOURHearing ability was tested by means of a click produced by striking a pair of forceps on a bottle. Refined methods were considered unnecessary as deafness could be recognised by this test without ambiguity in adult animals. Normal mice respond to it with a general muscular twitch which is most noticeable in the ear pinna. No such response was ever obtained in mice homozygous for deafness. The heterozygotes on the other hand were always normal, and the onset of hearing took place between io and 14 days depending on the size, general fitness and, perhaps, the genetic constitution of the individual. A number of the heterozygotes were kept until they were well over a year old and their hearing ability was found to be unimpaired.Though in general the behaviour of dn/dn is normal, tossing movements of the head have been observed in some individuals. This is a barely perceptible abnormality and can be best described as an accentuation of the normal sniffling movements. But it is quite distinct from the latter, especially to an observer familiar with the mutants of the shaker-waltzer type. GENETICSThe mutant gene dn was discovered in the curly-tail stock of this laboratory, its origin being independent of the ct gene. It must have been in that stock for some time as it was already fairly widely spread when first detected. The segregation data of table i show a close approximation to the ratios expected, if dii is a recessive gene with regular manifestation.It seems that the presence or absence of head tossing (HT) is influenced by the residual genotype. The data of table 2 show that, in matings between two dn/dn animals, the incidence of head tossing is lowest when neither parent, and highest when both parents toss their heads (x2 = 85II ; fl = 2 ; P = 0.015).463