Phenotypes associated with this allele

• Allele Symbol: Bcl2^tm1Sjk
• Allele Name: targeted mutation 1, Stanley J Korsmeyer
• Allele ID: MGI:1857134
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Bcl2^tm1Sjk/Bcl2^tm1Sjk	B6;129S2-Bcl2^tm1Sjk/J	MGI:3692964
hm2	Bcl2^tm1Sjk/Bcl2^tm1Sjk	involves: 129S2/SvPas * C57BL/6	MGI:2176718
cn3	Bcl2^tm1Sjk/Bcl2^tm1Sjk Tg(Dct-lacZ)A12Jkn/0	involves: 129S2/SvPas * C57BL/6 * C57BL/6J * CBA	MGI:6241340

Genotype
MGI:3692964

hm1

• Allelic Composition: Bcl2^tm1Sjk/Bcl2^tm1Sjk
• Genetic Background: B6;129S2-Bcl2^tm1Sjk/J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

muscle

abnormal skeletal muscle fiber type ratio ( J:66494 )

• although soleus and tibialis anterior muscles show similar numbers of slow myofibers as in wild-type, the number of fast myofibers is only about 2/3 the number in wild-type

Genotype
MGI:2176718

hm2

• Allelic Composition: Bcl2^tm1Sjk/Bcl2^tm1Sjk
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:15224 )

• onset of morbidity has a wide range, from 10 days to 10 weeks, with some surviving longer and to at least 19 weeks of age

postnatal lethality, incomplete penetrance ( J:15224 )

• the smallest mutants become noticeably ill and die after 1 week of age, however, the onset of morbidity has a wide range (10 days to 10 weeks), although there is a clustering at 2-3 weeks, just prior to weaning

embryo

increased metanephric mesenchyme apoptosis ( J:22552 )

• abundant TUNEL-positive apoptotic cells in E12 metanephroi, esp. within the mesenchymal regions

growth/size/body

round snout ( J:15224 )

• rounded snout

short snout ( J:15224 )

small ears ( J:15224 )

kidney cyst ( J:15224 , J:34504 , J:53123 )

• grossly enlarged kidneys are cystic (J:15224)

• small kidneys show small cysts (J:15224)

• relatively few cysts at P7; however, marked cyst formation between P21 and p28 (J:34504)

• at P21, cystic kidneys exhibit nuclear localization of beta-catenin and loss of apical brush border actin staining; however, protein levels of alpha-catenin, beta-catenin, actin, and E-cadherin are not altered in cystic kidneys relative to non-cystic kidneys (J:53123)

kidney cortex cyst ( J:22552 , J:34504 )

• detected at 1 week and 8 months of age (J:22552)

• cortex cysts of both proximal tubule and cortical collecting duct origin at P28 (J:34504)

kidney medulla cyst ( J:34504 )

• cysts originating from the medullary thick ascending limb of Henle's loop and the medullary collecting ducts at P28

polycystic kidney ( J:15224 , J:34504 )

• develop polycystic kidney disease (J:15224)

• after P7, cysts develop at mutliple sites along the nephron (J:34504)

decreased body size ( J:15224 )

• decreased body size is first seen at 1 week of age and varies from mutant to mutant

cachexia ( J:15224 )

• mutants that become visibly ill are often lethargic, anorectic, wasted, and at times tremulous

postnatal growth retardation ( J:15224 )

• growth rate slows after puberty

• exhibit immature facial features at 1 week of age

enlarged kidney ( J:15224 )

• kidneys are either grossly enlarged and cystic or small and pale

hearing/vestibular/ear

small ears ( J:15224 )

craniofacial

round snout ( J:15224 )

• rounded snout

short snout ( J:15224 )

small ears ( J:15224 )

immune system

increased T cell apoptosis ( J:15224 )

• thymocytes show accelerated cell death following an apoptotic stimulates (dexamethasone and radiation) compared to wild-type

abnormal thymus involution ( J:15224 )

• exhibit involution of thymus with aging and illness

increased double-negative T cell number ( J:15224 )

• increase in double negative CD4-CD8- thymocytes over time

decreased lymphocyte cell number ( J:15224 )

• the percent of lymphocytes and absolute lymphocyte count are decreased in the peripheral blood of ill mutants (lymphopenia)

decreased B cell number ( J:15224 )

• exhibit a loss of peripheral B cells over time due to increased apoptosis

decreased T cell number ( J:15224 )

• exhibit a loss of peripheral T cells over time due to increased apoptosis

decreased double-positive T cell number ( J:15224 )

• loss of CD4+CD8+ double positive thymocytes over time

abnormal CD4-positive, alpha beta T cell morphology ( J:15224 )

• total numbers of CD4+ single positive thymocytes decrease over time

abnormal CD8-positive, alpha beta T cell morphology ( J:15224 )

• total numbers of CD8+ single positive thymocytes decrease over time

abnormal immune system organ morphology ( J:15224 )

• exhibit massive cell death in lymphoid organs as mice age, especially the spleen and thymus, resulting in lymphoid organ involution

abnormal thymus morphology ( J:15224 )

• exhibit widespread apoptosis in thymus as mutants age and become ill

small thymus ( J:15224 )

• ill mutants exhibit a decrease in thymus size, with increased apoptosis in both cortex and medulla

abnormal spleen morphology ( J:15224 )

• spleen undergoes massive apoptotic involution with age

abnormal spleen red pulp morphology ( J:15224 )

• red pulp shows an increase in the proportion of erythroid relative to myeloid lineage cells

small spleen ( J:15224 )

• ill mutants exhibit a decrease in spleen size

abnormal spleen white pulp morphology ( J:15224 )

• loss of white pulp lymphoid areas with age and illness; many pyknotic and fragmented cells are noted in white pulp

renal/urinary system

increased kidney apoptosis ( J:34504 )

• increased apoptosis of cells within cysts and in the renal interstitium at P28, as shown by TUNEL staining

increased kidney cell proliferation ( J:15224 , J:34504 )

• mice exhibit hyperproliferative glomerular epithelial and interstitial components with increasing age (J:15224)

• 87-fold increase in the number of BrdU-positive cells detected in the medulla at P28 (J:34504)

• 1.9-fold increase in the number of BrdU-positive cells detected in the cortex at P28 (J:34504)

kidney cyst ( J:15224 , J:34504 , J:53123 )

• grossly enlarged kidneys are cystic (J:15224)

• small kidneys show small cysts (J:15224)

• relatively few cysts at P7; however, marked cyst formation between P21 and p28 (J:34504)

• at P21, cystic kidneys exhibit nuclear localization of beta-catenin and loss of apical brush border actin staining; however, protein levels of alpha-catenin, beta-catenin, actin, and E-cadherin are not altered in cystic kidneys relative to non-cystic kidneys (J:53123)

kidney cortex cyst ( J:22552 , J:34504 )

• detected at 1 week and 8 months of age (J:22552)

• cortex cysts of both proximal tubule and cortical collecting duct origin at P28 (J:34504)

kidney medulla cyst ( J:34504 )

• cysts originating from the medullary thick ascending limb of Henle's loop and the medullary collecting ducts at P28

polycystic kidney ( J:15224 , J:34504 )

• develop polycystic kidney disease (J:15224)

• after P7, cysts develop at mutliple sites along the nephron (J:34504)

enlarged kidney ( J:15224 )

• kidneys are either grossly enlarged and cystic or small and pale

parietal capsular epithelium metaplasia ( J:15224 )

• mice exhibit replacement of the normal flattened epithelium with a cuboidal proximal tubular epithelium and hyperplasia resulting in an immature epithelial crescent crowding the glomerulus, indicating tubular metaplasia of Bowman's epithelium

abnormal renal glomerulus morphology ( J:15224 )

• mice exhibit hyperproliferative glomerular epithelial components with increasing age

decreased renal glomerulus number ( J:22552 )

• fewer glomeruli are observed in neonatal kidneys relative to controls

abnormal metanephric mesenchyme morphology ( J:22552 )

• after 3 days in organ culture, tubulogenesis within the metanephric blastema is significantly reduced

• however, induction of the metanephric blastema occurs in vivo, with no significant differences in the size of metanephroi obtained from E12 mutant and control embryos

increased metanephric mesenchyme apoptosis ( J:22552 )

• abundant TUNEL-positive apoptotic cells in E12 metanephroi, esp. within the mesenchymal regions

abnormal metanephric ureteric bud development ( J:22552 )

• in organ culture, lack of nephrogenic development is confirmed by staining for lectin D. biflorus which stains the ureteric bud

small metanephros ( J:22552 )

• after 3 days in organ culture, growth and development of E12 mutant metanephroi is visibly reduced

abnormal nephrogenic zone morphology ( J:22552 )

• the size of nephrogenic zone is significantly reduced in neonatal kidneys

delayed kidney development ( J:34504 )

• after P7, kidney growth, as reflected by increased size and weight, is significantly slowed relative to wild-type controls

abnormal renal tubule epithelium morphology ( J:15224 )

• mitotic figures, not usually found in mature kidneys, are seen in the hyperplastic tubular epithelium

abnormal kidney interstitium morphology ( J:15224 )

• mice exhibit hyperproliferative interstitial components with increasing age

• kidneys have an abnormally abnundant interstitium that contains many cells with pyknotic nuclei within nests of immature appearing cells

increased compensatory renal growth ( J:34504 )

• by P21, unaffected glomeruli and non-cystic proximal tubules undergo compensatory growth

small kidney ( J:15224 , J:22552 )

• kidneys are either small and pale or grossly enlarged and cystic (J:15224)

• decreased kidney size at 1 week of age (J:22552)

• neonatal kidneys are not cystic but several-fold smaller than heterozygous control kidneys (J:22552)

decreased kidney weight ( J:34504 )

• approximately one-third of normal kidney weight at birth (P0)

renal hypoplasia ( J:22552 , J:34504 )

• renal hypoplasia at P0 (J:34504)

decreased nephron number ( J:22552 )

• reduced nephron number at birth

dilated distal convoluted tubule ( J:15224 )

• distal tubular ectasia (dilation) is apparent by 1 week after birth

dilated proximal convoluted tubule ( J:15224 )

• proximal tubular ectasia (dilation) is apparent by 1 week after birth

pale kidney ( J:15224 )

• small kidneys are pale

kidney failure ( J:22552 )

• severe renal insufficiency at 1-8 weeks of age, as shown by increased blood creatinine and BUN levels

homeostasis/metabolism

increased circulating creatinine level ( J:15224 , J:22552 )

• increases with age (J:15224)

increased blood urea nitrogen level ( J:15224 , J:22552 )

• increases with age (J:15224)

pigmentation

hypopigmentation ( J:15224 )

• hair turns gray with the second follicle cycle

• hypopigmentation often begins at the nose and proceeds caudally over 3-4 days

• hair shafts still demonstrate the differentially pigmented regions seen in wild-type, however they are markedly lightened throughout

• Fontana-Mason stain shows the presence of melanin in all hairs, suggesting a decrease in dark pigment rather than a loss of melanocytes

endocrine/exocrine glands

abnormal thymus morphology ( J:15224 )

• exhibit widespread apoptosis in thymus as mutants age and become ill

small thymus ( J:15224 )

• ill mutants exhibit a decrease in thymus size, with increased apoptosis in both cortex and medulla

abnormal primordial ovarian follicle morphology ( J:28173 )

♀ • numerous aberrantly formed primordial follicles with a single flattened layer of granulosa cells and lacking oocytes

♀ • normal primary, preantral, and antral follicles, containing normal oocytes

abnormal thymus involution ( J:15224 )

• exhibit involution of thymus with aging and illness

reproductive system

absent oocytes ( J:28173 )

♀ • loss of oocytes in aberrant primordial follicles

abnormal primordial ovarian follicle morphology ( J:28173 )

♀ • numerous aberrantly formed primordial follicles with a single flattened layer of granulosa cells and lacking oocytes

♀ • normal primary, preantral, and antral follicles, containing normal oocytes

hematopoietic system

increased T cell apoptosis ( J:15224 )

• thymocytes show accelerated cell death following an apoptotic stimulates (dexamethasone and radiation) compared to wild-type

abnormal thymus morphology ( J:15224 )

• exhibit widespread apoptosis in thymus as mutants age and become ill

small thymus ( J:15224 )

• ill mutants exhibit a decrease in thymus size, with increased apoptosis in both cortex and medulla

abnormal thymus involution ( J:15224 )

• exhibit involution of thymus with aging and illness

increased double-negative T cell number ( J:15224 )

• increase in double negative CD4-CD8- thymocytes over time

decreased lymphocyte cell number ( J:15224 )

• the percent of lymphocytes and absolute lymphocyte count are decreased in the peripheral blood of ill mutants (lymphopenia)

decreased B cell number ( J:15224 )

• exhibit a loss of peripheral B cells over time due to increased apoptosis

decreased T cell number ( J:15224 )

• exhibit a loss of peripheral T cells over time due to increased apoptosis

decreased double-positive T cell number ( J:15224 )

• loss of CD4+CD8+ double positive thymocytes over time

abnormal CD4-positive, alpha beta T cell morphology ( J:15224 )

• total numbers of CD4+ single positive thymocytes decrease over time

abnormal CD8-positive, alpha beta T cell morphology ( J:15224 )

• total numbers of CD8+ single positive thymocytes decrease over time

abnormal spleen morphology ( J:15224 )

• spleen undergoes massive apoptotic involution with age

abnormal spleen red pulp morphology ( J:15224 )

• red pulp shows an increase in the proportion of erythroid relative to myeloid lineage cells

small spleen ( J:15224 )

• ill mutants exhibit a decrease in spleen size

abnormal spleen white pulp morphology ( J:15224 )

• loss of white pulp lymphoid areas with age and illness; many pyknotic and fragmented cells are noted in white pulp

cardiovascular system

decreased vascular endothelial cell number ( J:96232 )

• exhibit a decreased number of endothelial cells in the retinas

abnormal retina vasculature morphology ( J:96232 )

• exhibit a significant decrease in retinal vascular density compared to wild-type; retinal vasculature contains less cellularity and fewer capillary loops

• exhibit delayed development and remodeling of retinal vasculature and a significant decrease in the number of major arteries, which branch off from near the optic nerve, however hyaloid vessel regression is not affected

• degree and extent of secondary and tertiary branching is compromised in retinal vasculature

• exhibit increased apoptosis and increased proliferation in the developing retinal vasculature

abnormal induced retina neovascularization ( J:96232 )

• degree of ischemia-induced retinal neovascularization is reduced, however show a similar sensitivity to hyperoxia-mediated vessel obliteration

abnormal pericyte morphology ( J:96232 )

• exhibit a decreased number of pericytes in retinas

vision/eye

abnormal retina vasculature morphology ( J:96232 )

• exhibit a significant decrease in retinal vascular density compared to wild-type; retinal vasculature contains less cellularity and fewer capillary loops

• exhibit delayed development and remodeling of retinal vasculature and a significant decrease in the number of major arteries, which branch off from near the optic nerve, however hyaloid vessel regression is not affected

• degree and extent of secondary and tertiary branching is compromised in retinal vasculature

• exhibit increased apoptosis and increased proliferation in the developing retinal vasculature

abnormal induced retina neovascularization ( J:96232 )

• degree of ischemia-induced retinal neovascularization is reduced, however show a similar sensitivity to hyperoxia-mediated vessel obliteration

cellular

absent oocytes ( J:28173 )

♀ • loss of oocytes in aberrant primordial follicles

abnormal cell adhesion ( J:53123 )

• at P21, cystic kidneys exhibit an altered distribution of beta-catenin and actin, suggesting that abnormal cell-cell adhesive interactions may contribute to cyst formation

increased T cell apoptosis ( J:15224 )

• thymocytes show accelerated cell death following an apoptotic stimulates (dexamethasone and radiation) compared to wild-type

increased metanephric mesenchyme apoptosis ( J:22552 )

• abundant TUNEL-positive apoptotic cells in E12 metanephroi, esp. within the mesenchymal regions

increased kidney apoptosis ( J:34504 )

• increased apoptosis of cells within cysts and in the renal interstitium at P28, as shown by TUNEL staining

increased kidney cell proliferation ( J:15224 , J:34504 )

• mice exhibit hyperproliferative glomerular epithelial and interstitial components with increasing age (J:15224)

• 87-fold increase in the number of BrdU-positive cells detected in the medulla at P28 (J:34504)

• 1.9-fold increase in the number of BrdU-positive cells detected in the cortex at P28 (J:34504)

Genotype
MGI:6241340

cn3

• Allelic Composition: Bcl2^tm1Sjk/Bcl2^tm1Sjk; Tg(Dct-lacZ)A12Jkn/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * C57BL/6J * CBA

embryo

abnormal melanoblast morphology ( J:157070 )

• mice show complete loss of LacZ+ melanoblasts in the bulge area at the end stage of hair follicle morphogenesis (i.e. stage 8, but not stage 6), indicating apoptosis of bulge melanocyte stem cells; in contrast, pigmented melanocytes are still maintained in the bulb at stage 8

• mice treated with an anti-TGF-beta blocking antibody during the process of stem cell entry to the dormant state (stage 5-8) exhibit increased survival (rescue) of bulge LacZ+ melanoblasts at P4, P6, and P8, whereas untreated mice or mice treated with a control antibody display virtual loss of LacZ+ melanoblasts from the bulge area by P8

nervous system

abnormal melanoblast morphology ( J:157070 )

• mice show complete loss of LacZ+ melanoblasts in the bulge area at the end stage of hair follicle morphogenesis (i.e. stage 8, but not stage 6), indicating apoptosis of bulge melanocyte stem cells; in contrast, pigmented melanocytes are still maintained in the bulb at stage 8

• mice treated with an anti-TGF-beta blocking antibody during the process of stem cell entry to the dormant state (stage 5-8) exhibit increased survival (rescue) of bulge LacZ+ melanoblasts at P4, P6, and P8, whereas untreated mice or mice treated with a control antibody display virtual loss of LacZ+ melanoblasts from the bulge area by P8