mortality/aging
• mice exhibiting growth retardation and other complications die at approximately 1 month of age
|
• 12.5% of mutants die on the day of birth
|
nervous system
• some sick mutants have subarachnoid hemorrhage
|
growth/size/body
• 10-20% smaller at birth
|
• evident shortly after birth in approximately 50% of the offspring
|
immune system
• increase in thymocyte apoptosis
|
• more than half of mutants show poor development of the thymus
|
• bone marrow shows reduction of pro-B, pre-B and immature B cells, with retention of mature B cells, suggesting that expansion of progenitor B cells is impaired
|
• in the bone marrow
|
• in the bone marrow
|
• percentage of granulocytes is increased
|
• increase in percentage of CD4- and CD8-single-positive cells
|
• numbers of thymocytes are decreased by 2-4-fold at birth
|
• decrease in the percentage of double-positive cells
|
• in the bone marrow
|
• percentage of monocytes is increased
|
• more than half of mutants show poor development of the spleen
|
• white pulp areas are decreased in spleen
|
• numbers of splenocytes are decreased by 2-8-fold at birth
|
skeleton
• very thin cranial bones
|
• short and thin limb bones
|
• partial disappearance of intervertebral disks with calcification in kinky tails
|
• bone densities of lumbar vertebrae in mutants with severe dwarfism at 32 days of age are nearly half those of wild-type
|
• bone densities of femurs in mutants with severe dwarfism at 32 days of age are nearly half those of wild-type
|
• retarded skeletogenesis
• growth of femoral trabecular and cortical bones is delayed at 17 and 32 days of age
|
• distal metaphyseal cartilaginous growth plates in the femurs show enlarged resting zones with thin proliferating and hypertrophic zones of chondrocytes
|
• thin proliferating zone in femurs
|
• reduced intramembranous ossification
|
hematopoietic system
• increase in thymocyte apoptosis
|
• more than half of mutants show poor development of the thymus
|
• bone marrow shows reduction of pro-B, pre-B and immature B cells, with retention of mature B cells, suggesting that expansion of progenitor B cells is impaired
|
• in the bone marrow
|
• in the bone marrow
|
• percentage of CD11b+Gr-1+ myeloid cells is increased in the bone marrow, indicating enrichment of mature granulocytes
• clonal culture assay of bone marrow cells shows that formation of GM colonies, megakaryocyte colonies, erythroid bursts, erythrocyte-Meg colonies and mixed hematopoietic colonies is reduced
|
• mild decrease in erythrocytes
|
• percentage of granulocytes is increased
|
• moderate reduction in platelets
|
• increase in percentage of CD4- and CD8-single-positive cells
|
• numbers of thymocytes are decreased by 2-4-fold at birth
|
• decrease in the percentage of double-positive cells
|
• in the bone marrow
|
• percentage of monocytes is increased
|
• more than half of mutants show poor development of the spleen
|
• white pulp areas are decreased in spleen
|
• numbers of splenocytes are decreased by 2-8-fold at birth
|
behavior/neurological
abnormal gait
(
J:82738
)
• some sick mutants exhibit uncoordinated gait
|
cardiovascular system
• some sick mutants have intra-abdominal hemorrhage
|
• some sick mutants have subarachnoid hemorrhage
|
limbs/digits/tail
• short and thin limb bones
|
kinked tail
(
J:82738
)
• half of mutants have kinked tails, observed as early as P4
|
respiratory system
• some sick mutants have pulmonary fibrosis
|
vision/eye
• some sick mutants have closed eyes even at 3 weeks of age
|
craniofacial
• very thin cranial bones
|
renal/urinary system
• poor development of the kidneys, with small and immature glomeruli
|
cellular
• increase in thymocyte apoptosis
|
endocrine/exocrine glands
• increase in thymocyte apoptosis
|
• more than half of mutants show poor development of the thymus
|
• numbers of thymocytes are decreased by 2-4-fold at birth
|