1Grüneberg ( 1966c) maintains that the structure of the hair is abnormal in a number of "color mutants" and cites as examples dilute, varitint-waddler, and grey-lethal. Although this awaits confirmation (other than the fact that the incorporation of nucleopetal melanocytes into the hair may cause local enlargement of the hair diameter see Chapter 4, Section I, D) it is not without precedent. It is well established that some, and probably all, of the alleles at the X-linked mottled ( Mo) locus affect hair structure (see Chapter 8), and there is some evidence that varitint-waddler ( Va), microphthalmia ( mi), and perhaps white ( Miwh) also act both in the melanoblast and in the hair follicle ( Mintz, 1971a; see Chapter 12, note 16).
2Inasmuch as recessive yellow ( e), unlike lethal yellow ( Ay), acts within the melanocyte (see Chapter 2, Section II, C, 3), the coat color of e/e;gl/gl animals might help resolve this question. If, on the one hand, the coats of such mice were indistinguishable from normal recessive yellow ( e/e;+/+ or e/e;gl/+) animals, this would indicate that gl probably does act in concert with the a-locus via the follicular environment. On the other hand, if gl/gl has a similar effect on recessive yellow as it has on lethal yellow, this would still leave its site of action unresolved, i.e., it could act via the follicular environment to alter phaeomelanin synthesis, or, it could act intracellularly along with e/e.
3The observation of Loutit and Sansom ( 1976) that the osteopetrotic defect of microphthalmic ( mi/mi) mice can be cured by inoculating them with cell suspensions containing hematopoietic stem cells from normal donors, even in the absence of X-irradiation ( Loutit, 1977), has led them to conclude that osteoclastic cells are derived through circulating monocytes from hematopoietic stem cells (see Chapter 12, note 5). If correct, this would undoubtedly hold for grey-lethal as well.
4Because subcutaneous injections of "thymocrescin," an extract prepared from calf's thymus, had no effect on grey-lethals it was concluded that the degeneration of the thymus was most likely the consequence of the poor condition of the animals, and not its cause ( Grüneberg, 1938).
5There are also two recessively inherited osteopetrotic conditions in mice which do not influence coat color: osteosclerotic ( oc) and osteopetrosis ( op). Animals homozygous for oc (chromosome 19) can be detected at 10 to 12 days of age by a circling behavior, odd clubbing shape of feet, and absence of teeth. Skeletal preparations show extra deposition of bone at the chondrocostal junction. There is likewise extra bone deposition in the hind limbs. Histologically there is no evidence of secondary bone resorption. The circling behavior becomes more pronounced with advancing age and most affected animals die at approximately 30 to 40 days of age. The double homozygote of this mutant and grey-lethal is viable ( Dickie, 1967a). Mice homozygous for osteopetrosis, which is linked to varitint-waddler on chromosome 12, are also recognizable at 10 days of age. They have no teeth, a short domed skull, short tail, and small body size. Compared with normal littermates, young op homozygotes "have excessive accumulations of bone without marrow cavities, increases in bone matrix formation and concentrations of parafollicular cells of the thyroid, and are hypophosphatemic" ( Marks and Lane, 1976). Their osteoclasts are small, few in number, and have an abnormal distribution of the lysosomal enzyme acid phosphatase in their cytoplasm. Nevertheless, this osteopetrotic condition is milder than that produced by gl/gl, mi/mi, and oc/oc. The main skeletal defect seems "to be a severe restriction in bone remodeling that is capable of slowly removing the excessive skeletal mass characteristic of the disease only after bone formation has declined to one-fifth that of normal littermates" ( Marks and Lane, 1976). If provided with adequate soft food op/op mice frequently survive weaning. Their breeding performance is, however, very poor ( Marks and Lane, 1976).
6The two loci are less than 1.2 cM apart. In fact, of a total of 256 chromosomes tested, no recombination between gr and mh was observed ( Lane and Deol, 1974).
7Hearing et al. ( 1973) also report that pallid affects melanization in the retina. However, according to these investigators although the number of granules in the adult retina is greatly reduced and their size diminished, they nevertheless display at least some melanin deposition. They also note that melanization in the choroid is affected.
8Another observation of Theriault and Hurley which deserves mentioning is that they found the morphology of a/a retinal and inner ear pigment granules to be strikingly similar; they both displayed a diversity in size and shape as well as an uneven melanization. Indeed, in their opinion, the inner ear melanocytes (melanosomes) seemed to resemble those of the retina more closely than those of the epidermis. This is somewhat surprising for whereas it is known the retinal melanocytes are formed in situ from the outer layer of the optic cup (see Chapter 1, note 4), those of the inner ear, like epidermal melanocytes, are of neural crest origin ( Markert and Silvers, 1956).
9Castle ( 1941, 1942; see also Grüneberg, 1952) also reported that pallid reduced body size more than pink-eyed. However, as in the case of dilute (see Chapter 4, note 2) the apparent effects which these coat-color determinants have on size could be due to closely linked genes.
10According to Erway et al. ( 1971) most pallid mice behave normally under cage conditions, except that about 25% of them display various degrees of head tilting. They also report that there is a clear correlation between their ability to swim normally with their otolith defects. The seriously affected pallid mice, when initially dropped into water, frequently exhibit a momentary tonic seizure, but then become coordinated and swim "in almost any direction, often undergoing tortous spiralling or back-circling because of the retracted position of the head." After they are removed from the water and placed on a solid surface, they often exhibit, temporarily, an exaggerated form of ataxia and head tilting, and sometimes they roll over repeatedly.
11Lyon ( 1955a, 1955b) reported that otolith matrix and crystals were first visible in the mouse between days 15.5 and 16.5 of gestation, and in these experiments manganese supplementation of pa mice was ineffective on the fourteenth day of gestation, or later, in preventing otolith defects. On the other hand, initiation of the supplement on the tenth or eleventh day of gestation produced results comparable to supplementation throughout gestation ( Erway et al., 1971).
12Sarvella ( 1954) also noted that although the viability of pearl mice until maturity is good when raised by pe/+ mothers, pearl females have smaller litters than pe/+ females, have a tendency to die during pregnancy and lactation, and are poor mothers.
13The behavior of pe in the 201 strain is very similar to the p-unstable ( pun) gene of the p-series ( Chapter 4, Section II, C, 9) as well as to four genes at the c-locus ( L. Russell, 1964). Two of these appear similar to c in phenotype (but one is homozygous lethal), and two are intermediate between c and ce. All of these, when either homozygous, or heterozygous with c, produce "a rather high frequency of animals with small dark (possibly full-colored) patches of fur," and one has produced a uniformly full-colored animal which transmitted C ( L. Russell, 1964). It also should be noted that at the a-locus somatic "reverse mutations" of the type a --> Aw have been observed ( Bhat, 1949; L. Russell, 1964). Both of these involved gonadal tissue. Frequent full-colored spots in mice heterozygous for Ames dominant spotting ( Wa) and white ( Miwh) have also been interpreted as a consequence of somatic reverse mutation ( Schaible and Gowen, 1960). No breeding results have been published for these animals (see Chapter 10, note 28 and Chapter 11, note 29).