B6By.Cg-Sox18^Ra Pt Os/J

Stock number: 000125
Research areas: Dermatology Research, Developmental Biology Research, Internal/Organ Research

Detailed description

The Sox18^Ra and Sox18^Ra-J alleles cause a less severe phenotype than the Sox18^Ra-Op allele. The Sox18^Ra and Sox18^Ra-J alleles are similar mutations and give a very similar phenotype. The Sox18^Ra allele has been more broadly described in the literature and will be covered here. Heterozygotes are viable and fertile. Heterozygotes have developmentally retarded sinus hair growth apparent at embryonic day 16.5 and retarded development of pelage follicles apparent by embryonic day 17.5. Thus, heterozygotes have slightly shorter vibrissae evident at birth, and can be distinguished at three days of age by their pink skin which, due to the abnormally sparse development of the coat, fails to darken like that of wildtype siblings. A paucity of fur is apparent by nine days of age and persists throughout life. Compared with the wild type pelage, Sox18^Ra/+ coats have longer guard hairs, shorter awls and zigzags, an increased number of guard hairs and awls, fewer zigzags, and no auchenes. There are mild morphological abnormalities in the hairs. There is no decrease in the number of hair follicles, but many of the follicles fail to grow hair. There is decreased yellow pigment in the hair causing the thin coat that develops to be darker than normal particularly in the dorsal midline. Subsequent to the first wave, hair growth is asynchronous and the normal cyclic fluctuations in skin thickness are not found. The adipose layer of the skin is thinner than normal. Despite this asynchrony of adjacent hair follicles, hair cycles do occur across the pelage, but are more diffuse than normal. The hair follicles have an aberrant shape and orientation. This aberrancy is more pronounced in homozygotes. The impact of the Sox18^Ra mutation on hair is more pronounced in the anterior regions than in the posterior regions. Approximately one in ten heterozygous pups displays chylous ascites, and the most severely affected do not survive. This trait is seen in males more than in females and is modified by genetic background. (Carter and Phillips, 1954; Slee, 1956 and 1957; Mann, 1963; Herbertson and Wallace, 1964; Wallace, 1979.)

Homozygotes are nearly bald, lack vibrissae, and usually die before weaning. They have generalized edema and weigh more at birth than wildtype littermates. It has been estimated that 40% of homozygotes die as embryos. The homozygotes that survive are often 5-10% shorter in body length. There are fewer hair follicles than normal and the few hairs that do grow have abnormal morphology. There is pigment in the tail and ear pinnae, and theear pinnae are thinner than normal and are often wrinkled. (Carter and Phillips, 1954; Slee, 1956 and 1957; Mann 1963.)

Allele

Symbol: Pt
Name: pintail
MGI accession ID: MGI:1861192
Generation method: Chemically induced (other)
Marker symbol: Pt
Marker name: pintail
Chromosome: 4
Strain of origin: PBR
Molecular note: This mutation was isolated at the Yale University School of Medicine in 1951.
General note: This mutation rose in a strain protractedly treated with methylcholanthrene (MCA).

Allele

Symbol: Sox18^Ra
Name: ragged
MGI accession ID: MGI:1856135
Generation method: Spontaneous
Synonyms: Ra
Marker symbol: Sox18
Marker name: SRY (sex determining region Y)-box 18
Chromosome: 2
Strain of origin: Translocation stock
Molecular note: A deletion of a cytosine residue introduced a frameshift mutation affecting amino acids downstream of 314. Translation was prematurely stopped at codon 435. The deleted nucleotide was reported as nucleotide 960 in J:61488 and as nucleotide 938 in J:74211 and J:83731.
General note: Sox18^ra, ragged, semidominant. Arose spontaneously in a crossbred stock. In heterozygotes the first coat develops a little more slowly than normal. The coat contains guard hairs and awls but no auchenes and very few zigzags. This gives the coat a thin ragged appearance. The agouti pattern is modified, the entire coat being unusually dark. Heterozygotes are normally viable and fertile. Homozygotes are almost completely naked. Many are edematous at birth, and almost all die before weaning. A few survive and may breed (J:86). Developmental studies have shown that in Sox18^ra/+ mice, growth of the late differentiating hair follicles which produce auchenes and zigzags is very retarded or arrested (J:12991). A low percentage of Sox18^ra/+ mice in some stocks were found by Herbertson and Wallace (J:13089) to have a white chylous fluid in the abdomen from shortly after birth until a week or so of age. The incidence of chylous ascites in these mice is affected by one or more genes unlinked to Sox18^Ra, and also by two mutant genes linked to Sox18^Ra, (fi, we) and one on a different chromosome (py, Chr 1) (J:6220).

The phenotypes of Sox18^Ra and Sox18^ra-J have been described as indistinguishable (J:51188).

Allele

Symbol: Os
Name: Os
MGI accession ID: MGI:1857646
Generation method: Radiation induced
Marker symbol: Os
Marker name: oligosyndactylism
Chromosome: 8
Strain of origin: (101 x C3H)F1
Molecular note: The oligosyndactylism mutation is due to a chromosomal inversion that has breakpoints approximately 10 Mb apart. One breakpoint appears to reside in the Anapc10 gene, and an aberrant transcript consisting of part of Anapc10 and an unrelated sequence is expressed at low levels.
General note: Heterozygotes are affected on all four feet. Fusion usually occurs between the second and third digits and occasionally involves the fourth (J:13049). The muscles of the forearms and lower legs as well as of the feet show anomalous arrangements not necessarily correlated with the skeletal changes (J:12944). At 11 days of gestation the preaxial border of the limbs can be seen to be reduced (J:12942), and a histological examination at this time shows that there is a small amount of cellular degeneration in the preaxial part of the footplate mesoderm, leading to coalescence of the second and third digital rudiments (J:5107). Os /+ mice have a mild diabetes insipidus present at 5 weeks and increasing with age. In combination with one or more recessive modifying genes in the selected DI stock, Os/+ mice have a severe diabetes insipidus (J:12948). The cause of the diabetes is a 45% reduction in size of the kidneys with an 80% reduction in number of glomeruli. Compensatory hypertrophy of the nephrons is not sufficient to restore normal urine-concentrating ability (J:5127)(J:5128).