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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Lrrc8atm1.1Geha
targeted mutation 1.1, Raif S Geha
MGI:5581436
Summary 1 genotype
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Lrrc8atm1.1Geha/Lrrc8atm1.1Geha B6.129S1(Cg)-Lrrc8atm1.1Geha MGI:5825472


Genotype
MGI:5825472
hm1
Allelic
Composition
Lrrc8atm1.1Geha/Lrrc8atm1.1Geha
Genetic
Background
B6.129S1(Cg)-Lrrc8atm1.1Geha
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lrrc8atm1.1Geha mutation (0 available); any Lrrc8a mutation (54 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Growth retardation, epidermal hyperkeratosis, thin skeletal muscle bundles, vacuolated renal tubular cells, and absence of ovarian corpora lutea in Lrrc8atm1.1Geha/Lrrc8atm1.1Geha mice

mortality/aging
• only very few homozygotes survive beyond 4 weeks and none survive beyond 16 weeks of age
• heterozygous matings yield ~7.9% of homozygous embryos (versus expected 25%) at E14.5
• only ~5.5% of live homozygous pups are recovered from heterozygous matings

growth/size/body
• significant reduction in body weight after P4
• however, feeding is normal
• although normal at birth, mice exhibit growth retardation by the end of the first postnatal week

reproductive system
• absence of ovarian corpora lutea
• mice are sterile

integument
• curly hair
• epidermal hyperkeratosis

behavior/neurological
• hind limb weakness

muscle
• thin skeletal muscle bundles

renal/urinary system
• progressive hydronephrosis
• vacuolated renal tubular cells

immune system
• numerous pyknotic and karyorrhectic nuclei in the thymus
• very thin thymus cortical layer
• effacement of the thymus corticomedullary junction
• disorganized thymus medulla
• markedly smaller thymus
• ~10-fold reduction in thymus cellularity
• marked reduction in thymocyte numbers
• significant decrease in DN2 thymocyte number at 3-6 weeks of age
• however, DN1 thymocyte number and distribution of DN1a-e subsets are normal
• significant decrease in DN3 thymocyte number at 3-6 weeks of age
• significant decrease in DN4 thymocyte number at 3-6 weeks of age
• marked reduction of AKT phosphorylation in thymocytes
• increased numbers of CD3+ cells that co-stain for activated caspase 3
• increased % of annexin V+ apoptotic thymocytes at 3-6 weeks of age
• increased numbers of TUNEL+ apoptotic cells in the thymus
• modest impairment in B cell development
• however, splenic B cells proliferate normally to anti-IgM, anti-CD40 and LPS, and antibody response to type I T-independent (TI) antigen (TNP-LPS) and to type II TI antigen (TNP-Ficoll) is normal, indicating intact B cell function
• modest decrease in the % of CD43-B220lowIgM+ immature B cells in the bone marrow
• modest decrease in the % of transitional B cells in spleen
• modest increase in the % of CD43+B220lowIgM- pro-B cells in the bone marrow
• severe cell-intrinsic block in early thymocyte development
• analysis of TCR-Vbeta CDR3 diversity in splenic T cells at 6 weeks of age revealed partial restriction of the T cell repertoire, as shown by skewed distribution for some (~25%), but not all, of the TCR-Vbeta families analyzed
• significant decrease in double-negative thymocytes at 3 weeks of age
• drastic decrease in double-positive thymocytes at 3 weeks of age
• modest decrease in the % of B220hi IgMhi recirculating B cells in the bone marrow
• ~4-fold reduction in the number of B220+ cells in spleen
• however, % of splenic B220+AnnexinV+ cells is normal
• numbers and subset distribution of peritoneal B220+ B cells are normal
• modest decrease in the % of marginal zone B cells in spleen
• however, % of splenic follicular B cells is normal
• modest decrease in the % of CD43-B220lowIgM- pre-B cells in the bone marrow
• significant increase in the % of CD4+ FOXP3+ regulatory T cells in the thymus
• significant reduction in the number of T cells in spleen
• however, the CD4/CD8 ratio and % of splenic CD3+ Annexin V+ cells are normal
• significant decrease in single-positive thymocytes at 3 weeks of age
• significant decrease in single-positive thymocytes at 3 weeks of age
• small spleens with well-preserved architecture
• increased serum IgG2a levels at 4-6 weeks of age
• however, serum levels of IgM, IgA, and IgG1, IgG2b and IgG3 isotypes are normal
• impaired peripheral T cell function
• marked decrease in % of BrdU+ thymocytes at 3-6 weeks of age
• impaired proliferation of splenic T cells to immobilized anti-CD3, not increased by the addition of anti-CD28 mAb or IL-2

endocrine/exocrine glands
• numerous pyknotic and karyorrhectic nuclei in the thymus
• very thin thymus cortical layer
• effacement of the thymus corticomedullary junction
• disorganized thymus medulla
• markedly smaller thymus
• ~10-fold reduction in thymus cellularity
• marked reduction in thymocyte numbers
• significant decrease in DN2 thymocyte number at 3-6 weeks of age
• however, DN1 thymocyte number and distribution of DN1a-e subsets are normal
• significant decrease in DN3 thymocyte number at 3-6 weeks of age
• significant decrease in DN4 thymocyte number at 3-6 weeks of age
• absence of ovarian corpora lutea
• marked reduction of AKT phosphorylation in thymocytes
• increased numbers of CD3+ cells that co-stain for activated caspase 3
• increased % of annexin V+ apoptotic thymocytes at 3-6 weeks of age
• increased numbers of TUNEL+ apoptotic cells in the thymus

hematopoietic system
• numerous pyknotic and karyorrhectic nuclei in the thymus
• very thin thymus cortical layer
• effacement of the thymus corticomedullary junction
• disorganized thymus medulla
• markedly smaller thymus
• ~10-fold reduction in thymus cellularity
• marked reduction in thymocyte numbers
• significant decrease in DN2 thymocyte number at 3-6 weeks of age
• however, DN1 thymocyte number and distribution of DN1a-e subsets are normal
• significant decrease in DN3 thymocyte number at 3-6 weeks of age
• significant decrease in DN4 thymocyte number at 3-6 weeks of age
• marked reduction of AKT phosphorylation in thymocytes
• increased numbers of CD3+ cells that co-stain for activated caspase 3
• increased % of annexin V+ apoptotic thymocytes at 3-6 weeks of age
• increased numbers of TUNEL+ apoptotic cells in the thymus
• modest impairment in B cell development
• however, splenic B cells proliferate normally to anti-IgM, anti-CD40 and LPS, and antibody response to type I T-independent (TI) antigen (TNP-LPS) and to type II TI antigen (TNP-Ficoll) is normal, indicating intact B cell function
• modest decrease in the % of CD43-B220lowIgM+ immature B cells in the bone marrow
• modest decrease in the % of transitional B cells in spleen
• modest increase in the % of CD43+B220lowIgM- pro-B cells in the bone marrow
• severe cell-intrinsic block in early thymocyte development
• analysis of TCR-Vbeta CDR3 diversity in splenic T cells at 6 weeks of age revealed partial restriction of the T cell repertoire, as shown by skewed distribution for some (~25%), but not all, of the TCR-Vbeta families analyzed
• modest decrease in the % of B220hi IgMhi recirculating B cells in the bone marrow
• ~4-fold reduction in the number of B220+ cells in spleen
• however, % of splenic B220+AnnexinV+ cells is normal
• numbers and subset distribution of peritoneal B220+ B cells are normal
• modest decrease in the % of marginal zone B cells in spleen
• however, % of splenic follicular B cells is normal
• modest decrease in the % of CD43-B220lowIgM- pre-B cells in the bone marrow
• significant increase in the % of CD4+ FOXP3+ regulatory T cells in the thymus
• significant reduction in the number of T cells in spleen
• however, the CD4/CD8 ratio and % of splenic CD3+ Annexin V+ cells are normal
• significant decrease in double-negative thymocytes at 3 weeks of age
• drastic decrease in double-positive thymocytes at 3 weeks of age
• significant decrease in single-positive thymocytes at 3 weeks of age
• significant decrease in single-positive thymocytes at 3 weeks of age
• small spleens with well-preserved architecture
• increased serum IgG2a levels at 4-6 weeks of age
• however, serum levels of IgM, IgA, and IgG1, IgG2b and IgG3 isotypes are normal
• impaired peripheral T cell function
• marked decrease in % of BrdU+ thymocytes at 3-6 weeks of age
• impaired proliferation of splenic T cells to immobilized anti-CD3, not increased by the addition of anti-CD28 mAb or IL-2

cellular
• increased numbers of CD3+ cells that co-stain for activated caspase 3
• increased % of annexin V+ apoptotic thymocytes at 3-6 weeks of age
• increased numbers of TUNEL+ apoptotic cells in the thymus
• marked decrease in % of BrdU+ thymocytes at 3-6 weeks of age
• impaired proliferation of splenic T cells to immobilized anti-CD3, not increased by the addition of anti-CD28 mAb or IL-2

homeostasis/metabolism
N
• serum levels of TNF and cortisol are normal





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last database update
12/17/2024
MGI 6.24
The Jackson Laboratory