SSL/LeJ

Stock number: 000308
Product name: piebald lethal
Research areas: Dermatology Research, Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research, Sensorineural Research

Description

This inbred strain carries two segregating alleles of piebald, Ednrb^s and Ednrb^s-l (piebald lethal). Piebald mice are characterized by irregular white spotting.

Detailed description

This inbred strain carries both the piebald (Ednrb^s) and piebald lethal (Ednrb^s-l) alleles. Homozygous piebald mice show irregular white spotting, the amount of which is greatly influenced by minor modifying genes. They also have dark eyes. Homozygous piebald lethal mice are almost completely white with dark eyes and only an occasional small pigmented spot on the head or rump. Piebald-piebald lethal heterozygotes (Ednrb^s/Ednrb^s-l) mice resemble piebald mice in the degree of spotting. The piebald mutations disrupt the development of melanocytes derived from the neural crest. All piebald lethal homozygotes develop megacolon with a lack of enteric ganglion cells in the posterior end of the colon. On the SSL/Le background, although many Ednrb^s-l homozygotes die between 2 and 4 weeks of age, significant numbers survive and may breed. The incidence of megacolon is reduced in piebald and piebald-piebald lethal heterozygotes and is affected by minor modifying genes.

Development

The piebald lethal mutation (Ednrb^s-l) arose spontaneously at The Jackson Laboratory in 1958 in a C3H/HeJ female showing a blaze and large belly spot. Piebald (Ednrb^s) is a very old mutation of the mouse fancy and came to The Jackson Laboratory from a Dr. Holman in 1955 in a multiple recessive stock called HO. The first piebald lethal female #133 was mated to a C57BL/6J male and the offspring were sibling mated. In 1962 a piebald lethal female at F10 was crossed to a WLHR/Le (Stock No. 000147) male at F16 and the new stock was balanced with Ednrb^s-l and hairless (Hr^hr) in repulsion. This stock was sibling mated, reaching F20 in 1968. In 1968 a piebald (a/a Endrb^s/Ednrb^s) female from a partially inbred line at F20 was mated to a Ednrb^s-l +/+ Hr^hr male at F20 and the piebald, piebald lethal (SSL) stock was started. This stock is homozygous for nonagouti (a/a) and segregating for piebald (Ednrb^s) and piebald lethal (Ednrb^s-l). It reached generation F47 in 1983 and F105 in 2005.

Allele

Symbol: a
Name: nonagouti
MGI accession ID: MGI:1855937
Generation method: Spontaneous
Marker symbol: a
Marker name: nonagouti
Marker synonyms: agouti; agouti signal protein; AGSW; AGTI; AGTIL; As; ASP; SHEP9
Chromosome: 2
Strain of origin: old mutant of the mouse fancy
Molecular note: Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for a^t-2Gso and A^w-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.
General note: Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039

Allele

Symbol: Ednrb^s
Name: piebald
MGI accession ID: MGI:1856148
Generation method: Spontaneous
Synonyms: pied spotting; s
Marker symbol: Ednrb
Marker name: endothelin receptor type B
Marker synonyms: ABCDS; Ednra; ETB; ET-B; ETB1; ETBR; ET-BR; ETRB; ETR-b; HSCR; HSCR2; Sox10m1; WS4A
Chromosome: 14
Strain of origin: old mutant of the mouse fancy
Molecular note: This mutation is allelic to a targeted mutation for this gene. Homozygous mice produce approximately 25% of the normal levels of transcript from this allele. RT-PCR analysis demonstrated that no alterations in the coding sequence would result in any alteration of the amino acid sequence. A 5.5 kb retrotransposon-like element is found in intron 1. About 75% of the mRNA produced is an aberrant 6.5 kb form lacking exons 2-6 but containing exon 1. The remaining 25% of the mRNA formed is of normal, 4.4 kb, size.
General note: Also called piebald spotting. This is a very old mutation of the mouse fancy, and was described in the scientific literature as early as 1920 (J23183). Some piebalds in existing stocks may be of independent origin.

Allele

Symbol: Ednrb^s-l
Name: piebald lethal
MGI accession ID: MGI:1856149
Generation method: Spontaneous
Synonyms: s^l
Marker symbol: Ednrb
Marker name: endothelin receptor type B
Marker synonyms: ABCDS; Ednra; ETB; ET-B; ETB1; ETBR; ET-BR; ETRB; ETR-b; HSCR; HSCR2; Sox10m1; WS4A
Chromosome: 14
Strain of origin: (C3H/HeJ x C57BL/6)F2
Molecular note: Southern blotting revealed that all of the coding exons of the gene were deleted. In addition, the transcript was undetectable by northern blotting in homozygous mice. The deletion encompasses 97,637 base pairs of chromosome 14, beginning 15.72 kb upstream of Ednrb and continuing 54.98 kb downstream. According to the Ensembl genome database (m37), no other genes are located in the region that is deleted.