A new allele of the lpr locus, lprcg, that complements the gld gene in induction of lymphadenopathy in the mouse.
Several mice with generalized lymphadenopathy were found in the CBA/KlJms (CBA) colony maintained at our institute. A new mutant strain of mice that develop massive lymphoid hyperplasia at 100% incidence within 5 mo after birth was established by crossing these diseased mice. Genetic studies on lymphadenopathy were conducted in F1, F2, and backcross populations from crosses between mutant CBA (CBA-m) and various inbred strains of mice. The results supported the control of lymphadenopathy by a single autosomal recessive gene. Since C3H/He-gld/gld (C3H-gld), MRL/MpJ-lpr/lpr (MRL-lpr), and C3H/HeJ-lpr/lpr (C3H-lpr) mice develop the same type of lymphoid hyperplasia, allelism of the mutant gene with gld or lpr was tested by investigating lymphadenopathy in F1 and backcross populations from crosses between CBA-m and C3H-gld, MRL-lpr, or C3H-lpr mice. The gene was confirmed to be allelic with lpr but not with gld. Interestingly, however, the mutant gene interacted with gld to induce less severe lymphadenopathy. Thus, the mutant gene was named lprcg, an lpr gene complementing gld in induction of lymphoproliferation. The genetic conclusion was supported by the same profile of surface markers of lymphoid cells with gld/gld, lpr/lpr, lprcg/lprcg, lprcg/lpr, and +/gld +/lprcg genotypes, as well as by massive lymph node hyperplasia and high titers of autoantibodies in the first four genotypes, but slight hyperplasia and insignificant autoantibody production in the last. The discovery of lprcg provided strong genetic evidence for the parallels between anomalous phenotypes of gld and lpr, and CBA/KlJms-lprcg/lprcg mice will contribute to elucidation of the mechanism of induction of the same abnormal differentiation and functions of lymphocytes by gld and lpr.
Laboratory Animal Research Center, University of Tokyo, Japan.
A
A
Matsuzawa
T
T
Moriyama
T
T
Kaneko
M
M
Tanaka
M
M
Kimura
H
H
Ikeda
T
T
Katagiri
D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D004247:DNA / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006965:Hyperplasia; D007136:Immunoglobulins / Q000276:immunology; D008198:Lymph Nodes / Q000473:pathology; D008206:Lymphatic Diseases / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics; D009154:Mutation; D009929:Organ Size; D013154:Spleen / Q000473:pathology
D007136:Immunoglobulins; D004247:DNA