Chapter 11

Steel, Flexed-Tail, Splotch, and Varitint-Waddler

IV. Varitint-Waddler ( Va) and Varitint-Waddler-J ( Va^J)

There are two semidominant alleles at this locus on the twelfth chromosome. One of these, Va, occurred in 1942 at the Jackson Laboratory ( Cloudman and Bunker, 1945) and the other, Va^J, in 1967 at the same laboratory ( Lane, 1972).

A. Varitint-Waddler ( Va)

Va was observed first in two offspring of a (C57BL x C57BR)F₁ female (one in each of her first two litters) which was backcrossed to a C57BL male. Inasmuch as the male produced numerous normal but no abnormal young when mated to other females, it seems likely that the mutation arose in the mother and that she was a germinal mosaic ( Cloudman and Bunker, 1945).

1. General Characteristics

The mutation combines a peculiar type of variegated pigment pattern with a modified shaker-syndrome ( Grüneberg, 1952). All Va mice are deaf and show circling behavior, head tossing, and hyperactivity. These behavioral abnormalities are more marked in homozygotes than in heterozygotes.

While the viability of the Va/+ heterozygote is nearly normal, homozygous Va mice are greatly reduced in number presumably because a considerable number of them die before birth ( Cloudman and Bunker, 1945).

Most Va homozygotes and some heterozygous males are sterile, and female heterozygotes often make poor mothers.

2. Influence on Coat Color and Hair Structure: A Complex Locus?

The coats of young Va heterozygotes display a combination of spotting with dilution ( Plate 3G; Figures 11-2 and 11-3c). There are some islands of fur, some large, others small, which are pigmented intensely. These never cross the midline of the body either dorsally or ventrally and do not seem to change with age. Other regions of the coat show a dilute pigmentation. These areas become fainter as the animal gets older and ultimately end up white or nearly so. Finally, some regions including most of the belly are nonpigmented from the beginning although occasionally fully pigmented areas extend to the mid-ventral line ( Cloudman and Bunker, 1945; Grüneberg, 1952; see note 29).

Va heterozygotes are detectable at about 3 days of age when scattered white areas appear on the head and body. These areas have a very broken pattern and sometimes there is an intermingling of white and colored hairs giving an appearance that might be called roan ( Cloudman and Bunker, 1945).

According to Mintz ( 1971a) the pigment patterns displayed by Va/+ mice can be attributed to both melanoblast and hair follicle phenoclones occurring simultaneously (see Chapter 7). Indeed, in her opinion "there are some inviable melanoblast clones and also two phenotypic colors of viable clones, yielding a three-color melanoblast pattern." It thus appears that Va, like mottled ( Mo), may be a complex locus.

Grüneberg ( 1966c) draws attention to the fact that the pigment patterns of Va/+ mice resemble some of the patterns produced by the Mo series of alleles (see Chapter 8, Section II). Moreover, he reports that, as in the case of the Mo-series, both hair structure and melanin formation are affected. "The white hairs are grossly abnormal in structure, the grey ones rather less so, whereas the normally pigmented hairs are structurally nearly, but apparently not quite, normal." It is his contention that the defective pigmentation of Va/+ animals is secondary to abnormal hair structure, and that the color changes with age reflect a gradual deterioration of hair structure. ²⁹

Va/Va mice are white except for small patches of unaltered colored hairs which usually occur near the ears and the base of the tail. ³⁰ At birth these animals are very pale but there is no evidence that they are anemic [although Grüneberg ( 1952) believes this may need verification].

3. Interaction With Other Spotting Determinants

As is the case with many of the other spotting genes there is a striking interaction when Va/+ is combined with either dominant spotting ( W) or viable dominant spotting ( W^v). Thus the double heterozygotes Va/+;W/+ and Va/+;W^v/+ are nearly completely white except for some pigmented spots on the head and near the tail ( Cloudman and Bunker, 1945; Grüneberg, 1952). This synergism evidently does not occur between Va/+ and piebald spotting ( s/s) since preliminary data indicate that Va/+;s/s and Va/+;s/+ genotypes may be phenotypically difficult to separate ( Cloudman and Bunker, 1945).

4. Behavior and Relationship to Inner Ear Abnormalities

The behavior of Va homozygotes and heterozygotes has been described by Cloudman and bunker. At about 2 weeks of age Va/Va mice are very excitable. They are deaf but react quickly and violently when disturbed. Usually they begin by rolling over and over. This is followed by their jumping wildly into the air and finally by a convulsive stiffening of the body. These convulsions may account for the loss of many Va homozygotes under 1 month of age. Quite often young Va/Va mice do not right themselves when turned upside down gently ( Deol, 1954). Va heterozygotes are not as excitable and do not display a tendency to roll and leap; otherwise both Va/Va and Va/+ behave very much alike. When awake they are usually constantly in motion, nodding and tossing their heads. When walking they waddle (hence their name) and when excited they run in circles sometimes clockwise and sometimes counterclockwise. Although all Va/Va mice and elderly Va/+ animals, i.e., those over 10 months of age, cannot swim, young heterozygotes swim easily in small circles ( Cloudman and Bunker, 1945; Deol, 1954).

The inner ear of varitint-waddlers has been studied in detail by Deol ( 1954) and while lesions in the labyrinth ³¹ can explain their deafness it cannot account for all of their behavioral disorders. According to Deol, the shaking of the head may be "due to loss of tone in the neck muscles resulting from the defects of the utricular macula and the ampullary cristae or it may be central in origin."

B. Varitint-Waddler-J ( Va^J)

1. Origin and General Characteristics

This mutation, which has been described by Lane ( 1972), occurred in a male which was heterozygous for Va. All indications are that he was both a germinal and a somatic mosaic for Va/+ and Va^J (and hence that Va^J arose as a mutation from Va). He was originally classified as Va/+ but was not as varicolored as these mice should be. Because of his unusual color he was mated to a C57BL/6J (+/+) female. This mating produced not only Va/+ and +/+ mice, as expected, but a third phenotype as well. This new phenotype ( Va^J/+) is characterized by "a slightly diluted coat color, a large irregular belly spot, white feet, and a white tail tip, closely resembling the viable dominant spotting heterozygote, W^v/+" ( Figure 11-3b). Although Va^J/+ mice are deaf they behave normally.

Va^J/Va^J mice have a dilute coat color and are predominantly white ( Figure 11-3d). They are deaf but swim and behave normally. Both sexes are fertile.

A considerable number of Va/Va^J mice, like Va homozygotes, evidently die in utero as only a dozen such mice (four of which died young) occurred in 231 progeny of Va/+ x Va^J/+ matings. Such heterozygotes are somewhat similar to the Va^J homozygote but are smaller with more white spotting. They are also deaf, cannot swim, and circle vigorously.

Clearly the Va-locus is among the more interesting coat color determinants and as such merits further attention.