Phenotypes Associated with This Genotype

Genotype
MGI:4941623

hm3

• Allelic Composition: Hoxa5^tm1Rob/Hoxa5^tm1Rob
• Genetic Background: involves: 129S/SvEv * C57BL/6 * MF1

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

respiratory system

lung inflammation ( J:113378 )

• chronic lung inflammation, including goblet cell hyperplasia, mucus hypersecretion, and recruitment of inflammatory cells is observed

• a significantly higher number of macrophages, lymphocytes and neutrophils is detected in the bronchoalveolar lavage fluid (BALF) relative to that in wild-type controls

• mutant BALF contains large, vacuolated macrophages with dark inclusions, not seen in control samples

• most macrophages stain positively for MMP-12, suggesting increased elastase production in mutant lungs

• inflammatory response is associated with slightly elevated MMP2 and MMP9 activities in alveolar macrophage-conditioned medium

impaired lung alveolus development ( J:113378 )

• at P5, very few growing septa are observed, indicating impaired alveolar septation

• at P15, only some alveoli are formed unlike in wild-type lungs

abnormal lung weight ( J:113378 )

• at P0, P5, and P15, the lung weight/body weight ratio is lower than that in wild-type controls; however, this difference is resolved by P31

• lung proliferation is initially reduced (P0 and P5) but subsequently higher than that in wild-type lungs (P15 and P31), with no significant differences noted at P60

• no significant differences in lung apoptosis are observed at any postnatal stage tested

abnormal pulmonary alveolus morphology ( J:113378 )

• at P31, some areas of mutant lungs are completely depleted of alveoli, whereas others display large tubular structures

atelectasis ( J:113378 )

• at P0, mutant lungs are collapsed unlike wild-type lungs

• at P15 and P31, areas of atelectasis are observed

overexpanded pulmonary alveolus ( J:113378 )

• at P15, enlarged distal airspaces are observed

abnormal pulmonary interalveolar septum morphology ( J:113378 )

• at P5, very few growing septa are observed unlike in wild-type lungs

emphysema ( J:113378 )

• at P31 and P60, an emphysema-like phenotype is observed

abnormal pulmonary alveolar parenchyma morphology ( J:113378 )

• at P0, mutant lungs are collapsed with a thickened parenchymal layer

• at P5 and P15, alveolar myofibroblasts are abnormally trapped in the parenchyma surrounding alveoli rather than found at the tip of the growing septa as in wild-type lungs

• abnormal positioning of alveolar myofibroblasts results in improper elastin deposition and septa formation

abnormal alveolar macrophage morphology ( J:113378 )

• a significantly higher percentage of alveolar macrophages is observed from birth to adulthood, except for P15

• at P31 and P60, an accumulation of vacuolated (hypertrophic and foamy) alveolar macrophages is observed, indicating an inflammatory response

increased type II pneumocyte number ( J:113378 )

• at P31, a small but significant increase in the number of Foxa2-positive type II pneumocytes is observed

abnormal pulmonary elastic fiber morphology ( J:113378 )

• at P0 and P5, pulmonary elastic fibers appear tangled in the parenchyma

• at P15 onwards, elastic fibers appear more abundant, disorganized and fragmented than in wild-type lungs

abnormal respiratory mucosa goblet cell morphology ( J:113378 )

• ectopic goblet cells are detected in distal structures such as the secondary bronchi and bronchioles, unlike in wild-type lungs

• specification of goblet cells is altered, resulting in hyperplasia, metaplasia, and mucus hypersecretion from P15 onwards

increased respiratory mucosa goblet cell number ( J:113378 )

• a striking increase in goblet cell number is noted along the epithelium of the trachea and the primary bronchi from P15 onwards, unlike in wild-type lungs

• increased goblet cell numbers are already evident at E18.5

abnormal surfactant secretion ( J:113378 )

• reduced surfactant protein production as a result of decreased surfactant protein gene expression, not due to a change in cellularity

immune system

abnormal alveolar macrophage morphology ( J:113378 )

• a significantly higher percentage of alveolar macrophages is observed from birth to adulthood, except for P15

• at P31 and P60, an accumulation of vacuolated (hypertrophic and foamy) alveolar macrophages is observed, indicating an inflammatory response

lung inflammation ( J:113378 )

• chronic lung inflammation, including goblet cell hyperplasia, mucus hypersecretion, and recruitment of inflammatory cells is observed

• a significantly higher number of macrophages, lymphocytes and neutrophils is detected in the bronchoalveolar lavage fluid (BALF) relative to that in wild-type controls

• mutant BALF contains large, vacuolated macrophages with dark inclusions, not seen in control samples

• most macrophages stain positively for MMP-12, suggesting increased elastase production in mutant lungs

• inflammatory response is associated with slightly elevated MMP2 and MMP9 activities in alveolar macrophage-conditioned medium

hematopoietic system

abnormal alveolar macrophage morphology ( J:113378 )

• a significantly higher percentage of alveolar macrophages is observed from birth to adulthood, except for P15

• at P31 and P60, an accumulation of vacuolated (hypertrophic and foamy) alveolar macrophages is observed, indicating an inflammatory response