STOCK Large2^{tm1(KOMP)Wtsi}/KcamJ

Stock number: 029923
Product name: Large2^-
Research areas: Neurobiology Research

Description

This strain carries a lacZ reporter-tagged knock-out allele of the mouse Large2 (Gyltl1b) gene, shown to contribute to the functional modification of α-dystroglycan in vivo.

Detailed description

Mutations in the human LARGE1 gene have been identified in congenital muscular dystrophy (CMD) patients with brain abnormalities. Both LARGE1 and paralog LARGE2 (LARGE xylosyl- and glucuronyltransferase 2; also called GYLTL1B) contribute to the functional modification of α-dystroglycan in vivo.

These targeted mutant mice carry a knock-out/lacZ reporter of the mouse Large2 gene. Homozygous knock-out mice are born at the expected Mendelian ratio when heterozygous mice are bred, and show no breeding or fertility problems. They appear healthy and are indistinguishable from their heterozygous and wildtype littermates with respect to body weight and life span when aged up to one year. No increase in spontaneous tumor load has been observed.

In cases of skeletal muscle, heart, and brain, the functional modification of α-dystroglycan in the knock-out mouse is comparable to that in the wildtype mouse. In kidneys, however, the functional modification of α-dystroglycan is diminished.

LARGE2/lacZ staining has been demonstrated in the kidney (loop of Henle, but not in the renal capsule), exocrine pancreatic cells (but not in endocrine islet cells), lung respiratory epithelium, maturing spermatocytes, and spermatozoa. LARGE2/lacZ expression is not found in skeletal muscle, the thymus, or small intestine.

Development

Mutant KOMP embryonic stem (ES) cell clone EPD0387_6_B09 was used to generate this mutant strain of mice. In this cell line, a targeting cassette containing the following replaced exons 4-11 (~3.3 kb) via homologous recombination in C57BL/6N-A^tm1Brd-derived JM8A3.N1 ES cells: FRT-splice acceptor (SA)-IRES-lacZ-polyA-loxP-β actin/neo-polyA-FRT-loxP. The ES cells were injected into blastocysts. The strain was backcrossed to C57BL/6J for 2-3 generations by the donating laboratory. Mice are black in color.

Allele

Symbol: Large2^{tm1(KOMP)Wtsi}
Name: targeted mutation 1, Wellcome Trust Sanger Institute
MGI accession ID: MGI:4419876
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Large2
Marker name: LARGE xylosyl- and glucuronyltransferase 2
Marker synonyms: 5730485C17Rik; GYLTL1B; PP5656
Chromosome: 2
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: The insertion of the L1L2_Bact_P cassette created a deletion of size 3304 starting at position 92197340 and ending at position 92200644 of Chromosome 2 (Genome Build GRCm39). This deletion results in the removal of functionally critical exon(s). The cassette is composed of an FRT site followed by lacZ sequence and a loxP site. This first loxP site is followed by a neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site.