Mouse Genome Informatics
hm1
    Bcl2tm1Sjk/Bcl2tm1Sjk
B6;129S2-Bcl2tm1Sjk/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
• 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


Mouse Genome Informatics
hm2
    Bcl2tm1Sjk/Bcl2tm1Sjk
involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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
• 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

growth/size
• decreased body size is first seen at 1 week of age and varies from mutant to mutant
• mutants that become visibly ill are often lethargic, anorectic, wasted, and at times tremulous
• growth rate slows after puberty
• exhibit immature facial features at 1 week of age

hearing/vestibular/ear

craniofacial
• rounded snout

immune system
• thymocytes show accelerated cell death following an apoptotic stimulates (dexamethasone and radiation) compared to wild-type
• increase in double negative CD4-CD8- thymocytes over time
• the percent of lymphocytes and absolute lymphocyte count are decreased in the peripheral blood of ill mutants (lymphopenia)
• exhibit a loss of peripheral B cells over time due to increased apoptosis
• exhibit a loss of peripheral T cells over time due to increased apoptosis
• loss of CD4+CD8+ double positive thymocytes over time
• total numbers of CD4+ single positive thymocytes decrease over time
• total numbers of CD8+ single positive thymocytes decrease over time
• exhibit involution of thymus with aging and illness
• exhibit massive cell death in lymphoid organs as mice age, especially the spleen and thymus, resulting in lymphoid organ involution
• spleen undergoes massive apoptotic involution with age
• red pulp shows an increase in the proportion of erythroid relative to myeloid lineage cells
• ill mutants exhibit a decrease in spleen size
• loss of white pulp lymphoid areas with age and illness; many pyknotic and fragmented cells are noted in white pulp
• exhibit widespread apoptosis in thymus as mutants age and become ill
• ill mutants exhibit a decrease in thymus size, with increased apoptosis in both cortex and medulla

renal/urinary system
• increased apoptosis of cells within cysts and in the renal interstitium at P28, as shown by TUNEL staining
• 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)
• 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
• mice exhibit hyperproliferative glomerular epithelial components with increasing age
• fewer glomeruli are observed in neonatal kidneys relative to controls
• 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
• abundant TUNEL-positive apoptotic cells in E12 metanephroi, esp. within the mesenchymal regions
• in organ culture, lack of nephrogenic development is confirmed by staining for lectin D. biflorus which stains the ureteric bud
• after 3 days in organ culture, growth and development of E12 mutant metanephroi is visibly reduced
• the size of nephrogenic zone is significantly reduced in neonatal kidneys
• after P7, kidney growth, as reflected by increased size and weight, is significantly slowed relative to wild-type controls
• mitotic figures, not usually found in mature kidneys, are seen in the hyperplastic tubular epithelium
• 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
• kidneys are either grossly enlarged and cystic or small and pale
• by P21, unaffected glomeruli and non-cystic proximal tubules undergo compensatory growth
• 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)
• approximately one-third of normal kidney weight at birth (P0)
• renal hypoplasia at P0 (J:34504)
• reduced nephron number at birth
• distal tubular ectasia (dilation) is apparent by 1 week after birth
• proximal tubular ectasia (dilation) is apparent by 1 week after birth
• 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)
• 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)
• cysts originating from the medullary thick ascending limb of Henle's loop and the medullary collecting ducts at P28
• develop polycystic kidney disease (J:15224)
• after P7, cysts develop at mutliple sites along the nephron (J:34504)
• small kidneys are pale
• severe renal insufficiency at 1-8 weeks of age, as shown by increased blood creatinine and BUN levels

homeostasis/metabolism
• increases with age (J:15224)
• increases with age (J:15224)

pigmentation
• 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
• numerous aberrantly formed primordial follicles with a single layer of granulosa cells and lacking oocytes (J:28173)
• normal primary, preantral, and antral follicles, containing normal oocytes (J:28173)

reproductive system
• numerous aberrantly formed primordial follicles with a single layer of granulosa cells and lacking oocytes (J:28173)
• normal primary, preantral, and antral follicles, containing normal oocytes (J:28173)
• loss of oocytes in aberrant primordial follicles (J:28173)

hematopoietic system
• thymocytes show accelerated cell death following an apoptotic stimulates (dexamethasone and radiation) compared to wild-type
• increase in double negative CD4-CD8- thymocytes over time
• the percent of lymphocytes and absolute lymphocyte count are decreased in the peripheral blood of ill mutants (lymphopenia)
• exhibit a loss of peripheral B cells over time due to increased apoptosis
• exhibit a loss of peripheral T cells over time due to increased apoptosis
• loss of CD4+CD8+ double positive thymocytes over time
• total numbers of CD4+ single positive thymocytes decrease over time
• total numbers of CD8+ single positive thymocytes decrease over time
• spleen undergoes massive apoptotic involution with age
• red pulp shows an increase in the proportion of erythroid relative to myeloid lineage cells
• ill mutants exhibit a decrease in spleen size
• loss of white pulp lymphoid areas with age and illness; many pyknotic and fragmented cells are noted in white pulp
• exhibit widespread apoptosis in thymus as mutants age and become ill
• ill mutants exhibit a decrease in thymus size, with increased apoptosis in both cortex and medulla
• exhibit involution of thymus with aging and illness

cardiovascular system
• exhibit a decreased number of endothelial cells in the retinas
• exhibit a decreased number of pericytes in retinas
• 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
• degree of ischemia-induced retinal neovascularization is reduced, however show a similar sensitivity to hyperoxia-mediated vessel obliteration

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

cellular
• 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
• thymocytes show accelerated cell death following an apoptotic stimulates (dexamethasone and radiation) compared to wild-type
• increased apoptosis of cells within cysts and in the renal interstitium at P28, as shown by TUNEL staining
• abundant TUNEL-positive apoptotic cells in E12 metanephroi, esp. within the mesenchymal regions
• 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)