Scraggly, a new hair loss mutation on mouse Chromosome 19
Bruce J. Herron,
Elizabeth C. Bryda,
Stephanie A. Heverly,
Doris N. Collins,
Molecular Genetics Program, Laboratory of Developmental Genetics, Wadsworth Center, 120 New Scotland Avenue, P.O. Box 22002,
Albany, New York 12201-2002, USA
Department of Biomedical Sciences, State University of New York at Albany, Albany, New York 12201, USA
Dept. of Microbiology, Immunology & Molecular Genetics, Marshall University School of Medicine, Huntington, West Virginia 25704, USA
Received: 8 December 1998 / Accepted: 10 May 1999
Abstract. By use of chlorambucil, we have generated a mouse
mutation called scraggly (sgl) that exhibits skin and hair defects.
Homozygous mutant mice exhibit hair loss, skin defects, and ab-
normalities in sebaceous lipid composition. We have constructed a
high-resolution genetic map of mouse Chromosome (Chr) 19 that
links this mutation to the anonymous DNA marker D19Umi1. An
additional cross, (BALB/c × CAST/Ei) F
× BALB/c, was used to
map markers around this mutation as well as to map the potential
candidate genes, Fgf8 and Cyp17. Allelism tests between sgl and
asebia (ab), another hair loss mutation on mouse Chr 19, showed
that these genes were separate and distinct.
Hair growth abnormalities can result from a variety of mutations in
the mouse (Sundberg 1994). These can affect the fullness of the
coat as well as its texture and color. Several of these mutations
have known counterparts in humans (Sundberg 1994). For ex-
ample, the recent cloning of the gene mutation causing hairless
(Cachon-Gonzalez et al. 1994) has led to the identification of the
human homolog in an Iraqi family with familial alopecia univer-
salis (Ahmad et al. 1998). However, many of these genes are still
with no known human equivalent. This may be owing to our lack
of knowledge about the genes that cause alopecia in humans or
alternatively may be owing to the different phenotypes that the
mutations can cause.
Of the many genes that affect hair growth in the mouse, few
have additionally affected the sebaceous gland (Sundberg 1994).
The sebaceous glands are holocrine glands that secrete sebum into
the upper portion of the hair follicle where it acts as a lubricant to
the growing hair shaft (Hamilton 1974). Sebum is an oily secretory
product that is thought to provide water barrier function to the skin
and hair, and to have bacteriostatic properties (Hamilton et al.
1974). Some of the genes in the mouse that are known to affect
sebaceous glands are hairless (hr) and asebia (ab). The ab/ab
mouse begins to lose hair 2–3 weeks after birth, and has flaky skin
throughout life (Gates and Karasek 1965). Histological examina-
tion of ab/ab skin sections shows a thicker and less compact epi-
dermis, an increased number of mast cells in the skin, and under-
developed sebaceous glands (Brown and Hardy 1989; Gates and
Karasek 1965). This mutation has been mapped to mouse Chr 19
(Sweet and Lane 1978), but the gene product responsible for this
disorder has not been identified. In the hr/hr mouse, sebaceous
gland hypertrophy is seen at 30 days of age followed by an atrophy
of the glands after one year of age (Sundberg 1994).
In the process of experiments designed to generate recessive
visible mutations in the mouse with the drug chlorambucil (Fla-
herty et al. 1992), we have isolated a mutation causing an abnor-
mal skin and hair phenotype and have named it scraggly (sgl)
because of the mouse’s unkempt appearance. In a preliminary
study, this mutation was mapped to the distal half of Chr 19 and
was initially considered as a possible new allele of ab. In this
paper, we present data showing that this mutation is at a separate
and distinct locus from ab. We also present new information on the
phenotype of the sgl/sgl mouse, showing its effect on sebaceous
Materials and methods
The mutant stocks of sgl/sgl mice were bred and maintained at the
Wadsworth Center. The inbred strains, C57BL/6 (B6), C3H/HeJ (C3H),
BALB/cBy (BALB), and CAST/Ei (CAST) were either purchased from
The Jackson Laboratory or bred at the Wadsworth Center. Asebia-J (ab
) mice were a kind gift from Leonard Schultz. B6C3Fe-a/a-bm ep ru
(bm-ep-ru) stock mice were purchased from The Jackson Laboratory.
Krd/+ mice were a kind gift from Miriam Meisler.
The sgl mutation was generated in a mutagenesis
scheme involving chlorambucil and has been described previously (Fla-
herty et al. 1992). Briefly, a C3H male was given a dose of 8.5 mg/kg of
chlorambucil and mated to B6 females. Male progeny from this cross were
crossed to B6 females, and the resulting female progeny were backcrossed
to their fathers. Litters were observed for phenotypes at birth and at wean-
ing. The sgl mutation has since been placed on the B6 background.
Generation of the ep-sgl mouse line.
The ep-sgl mouse line was pro-
duced by crossing sgl/sgl mice with ep ru/ep ru (obtained from the bm ep
ru linkage stock) bearing the pale ears (ep) and ruby eyed (ru) phenotype
(Dunn 1945; Lane 1967). Progeny (ep + ru/+sgl +) were intercrossed, and
recombinant mice were isolated with the ep or ru phenotype alone (ep ?
+/ep + ru or+?ru/ep + ru). These recombinants were then crossed to
sgl/sgl mice. After this test cross, one mouse was recovered that had the
genotype, ep sgl +/+ sgl +. This mouse was then backcrossed to sgl/sgl
mice and the progeny intercrossed to obtain the ep-sgl mouse line (ep sgl
+/ep sgl +). This line was then maintained by brother-sister matings.
Three backcrosses were performed: the ep-sgl line was mated
to ep sgl/+ + mice where the wild type chromosome was derived from B6
in cross 1, and CAST in cross 2. A (BALB/CAST)F
× BALB normal
backcross was also typed for Chr 19 markers (cross 3).
Allelism tests between ab
and sgl were performed by
breeding sgl/sgl females with ab
mice were observed for
phenotype at birth, weaning, and 3 months of age. Allelism tests with Krd
were also performed by crossing Krd/+ mice with sgl/sgl mice. Mice were
confirmed to carry the Krd-bearing chromosome by presence of an accom-
panying transgene (see below; Keller et al. 1994).
Polymerase Chain Reactions (PCR).
PCR reactions were either done
on genomic DNA extracted from tail biopsies (Laird et al. 1991) or from
Correspondence to: L. Flaherty
Mammalian Genome 10, 864–869 (1999).
© Springer-Verlag New York Inc. 1999