Whiskers amiss, a new vibrissae and hair mutation near the Krt1
cluster on mouse Chromosome 11
Lydia A. Taylor, Muriel J. Harris, Diana M. Juriloff
Department of Medical Genetics, University of British Columbia, 6174 University Boulevard, Vancouver, British Columbia V6T 1Z3, Canada
Received: 13 October 1999 / accepted: 7 December 1999
Abstract. Whiskers amiss (wam) is a new spontaneous recessive
mutation in the SELH/Bc strain of mice that causes a phenotype of
askew, sometimes kinked or curled, breakable whiskers and di-
sheveled-appearing body hair, apparently owing to disoriented
guard hairs. Heterozygotes on three genetic backgrounds are in-
distinguishable from normal. Using informative SSLPs in the F
generation after crosses to two normal strains, we have mapped
wam to the region of the type I keratin cluster on Chromosome
(Chr) 11, within an approximately 6-cM segment according to the
current Mouse Genome Database (MGD) map position of flanking
SSLPs. Although several other hair mutations also map to the Krt1
region (Re, Rim3, Bda, Bsk), none has a hair and whisker pheno-
type similar to that of wam, and, because all are transmitted as
dominants, interpretable complementation tests could not be done.
Scabbing and tissue loss occur on the rims of the pinnae and tail tip
in some aging wam homozygotes, suggesting that wam maybean
animal model of a genetic ectodermal disorder. The SELH/Bc
strain background appears to have an unusually high rate of spon-
taneous mutation; wam is the sixth mutation to be described.
Novel spontaneous mutations still identify unrecognized genes in
mice and may provide homologs of human genetic syndromes. In
1994, in the SELH/Bc strain of mice, we noted two 4-week-old
pups that appeared disheveled, compared with their six littermates.
On closer examination we saw that they had abnormally curled and
mis-directed whiskers. Subsequent crosses of these individuals
with other SELH/Bc mice and intercrosses of their descendants
indicated that the phenotype of disheveled hair and askew whis-
kers is due to a Mendelian recessive mutation, here provisionally
named “whiskers amiss”, wam.
Although there are several previously described mutations in
mice that cause curled whiskers and abnormal hair (for example,
Ca, cpy, cw, fr, lt, Mo, Re, ro, wa1, wa2, Wc, we; Doolittle et al.
1996), the descriptions of the hair abnormalities in all the known
mutants seemed to differ from the phenotype that we observed in
wam homozygotes. In 1996, further studies were begun to define
the wam phenotype in detail and to map the new wam mutation.
The purpose of this paper is to report the wam mutation, a pre-
liminary description of its phenotype, and its mapping to mid-
distal Chr 11 in the region of the type I keratin (Krt1) cluster.
Materials and methods
The mice are maintained in our animal rooms in the Department of
Medical Genetics at the University of British Columbia under standard
conditions described previously (Juriloff et al. 1991). SELH/Bc is an in-
bred strain that has a high frequency of exencephaly (Juriloff et al. 1989;
Juriloff and Harris 1998) and an apparently high spontaneous mutation rate
(Juriloff et al. 1994; Hofmann et al. 1998). The new wam mutation is now
maintained by affected breeding pairs on the SELH/Bc background. LM/
Bc is an inbred strain that we have used previously in genetic mapping
studies of the exencephaly trait of SELH/Bc; informative SSLP loci at 10
to 20-cM intervals across the genome have been previously identified
(Gunn 1996). The mice of the AXB-10/Pgn inbred strain used in this study
were third-generation descendants of mice obtained from The Jackson
Laboratory (Bar Harbor, Maine). For DNA work, all mice were killed by
gas and tissues were stored immediately at −20°C.
Within the SELH/Bc strain, the external phenotypes of wam
homozygotes, heterozygotes, and normal homozygotes were compared
from birth to 8 months of age, with inspection by eye and low-power gross
microscopy. Autopsies to look for internal anatomical and tooth defects
were done on five female and four male 6 to 8-month-old homozygotes.
Standard 5-micron, paraffin-embedded, hematoxylin and eosin-stained,
histological sections were taken from selected tissue samples from skin of
wam/wam and wam/+ adult mice (“Wax-it Histology Services”, Vancou-
For comparison of homozygote and heterozygote phenotypes on the
various genetic backgrounds (SELH/Bc, F
from a cross with LM/Bc, and
from a cross with AXB-10/Pgn), the whiskers and hair of wam/wam and
wam/+ were observed at 2–4 weeks of age.
Segregation, penetrance, and genetic background.
penetrance of wam on the SELH/Bc background were observed from
crosses within the “whiskers amiss” lineage of the SELH/Bc breeding
colony. The segregation and penetrance on other genetic backgrounds were
observed in the F
progeny after outcrosses of “whiskers amiss”
SELH/Bc mice to two normal strains, LM/Bc and AXB-10/Pgn (see link-
age studies below).
In the first linkage study, a single homozygous wam
SELH/Bc male mouse was mated to a normal LM/Bc female, and their F
progeny were intercrossed to generate F
individuals who were scored at
3–6 weeks of age. The abnormally curled, mis-directed whisker trait was
used to identify wam homozygotes, except in two litters with “nibbled
whiskers” from social grooming (a trait from LM/Bc) in which the hair on
the belly was used to score individuals as wam/wam or normal. Tail tissue
was collected individually from 32 wam/wam F
individuals and from three
litters. Equal portions of liver tissue from these 32 mice were
also pooled in groups (2–4 individuals per group). These pooled samples
were used in a genome scan for association between the SELH/Bc alleles
at SSLP loci and the “whiskers amiss” trait, detectable as a strong excess
of SELH/Bc allele product (instead of 50%) under conditions that amplify
each allele equally. We began the genome scan with one SSLP marker
from near the middle of each chromosome. After evidence of linkage to
D11Mit14 had been obtained, the 32 wam/wam F
s were typed as indi-
viduals for D11Mit14 and for several nearby proximal and distal informa-
tive markers. Three complete F
litters (n ס 38) were typed for D11Mit14
to check for Mendelian segregation ratios.
A second linkage study, informative for SSLP markers from within the
Krt1 keratin gene cluster on Chr 11 (D11Mit123 and D11Mit59), was based
on the F
of a cross between wam/wam SELH/Bc and the normal AXB-Correspondence to: D.M. Juriloff; email: email@example.com
Mammalian Genome 11, 255–259 (2000).
© Springer-Verlag New York Inc. 2000