repro-4461.cs

    public class MainWindow : Window
    {
        public MainWindow()
        {
            this.InitializeComponent();
            this.AttachDevTools();
            DataContext = new ViewModel();

            var btn = this.FindControl<Button>("doit");
            btn.Click += (s, e) => ((ViewModel)DataContext).Foo();
        }

        private void InitializeComponent()
        {
            AvaloniaXamlLoader.Load(this);
        }
    }

    public enum MyEnum
    {
        One,
        Two,
    }

    public class ViewModel : ReactiveObject
    {
        public ViewModel()
        {
            Objects = new ObservableCollection<TestModel>
            {
                new TestModel(new MyObj { Value = MyEnum.One }),
                new TestModel(new MyObj { Value = MyEnum.Two }),
            };

            SelectedObject = Objects[0];
        }

        public ObservableCollection<TestModel> Objects { get; }

        TestModel _selectedObject;
        public TestModel SelectedObject 
        {
            get => _selectedObject;
            set => this.RaiseAndSetIfChanged(ref _selectedObject, value);
        }

        public void Foo()
        {
            foreach (TestModel obj in Objects)
            {
                obj.Dispose();
            }
            SelectedObject = null;
            Objects.Clear();
        }
    }

    public class MyObj
    {
        public MyEnum Value { get; set; }
    }

    public sealed class TestModel : INotifyPropertyChanged, IDisposable
    {
        private void OnPropertyChanged(string property)
        {
            PropertyChanged?.Invoke(this, new PropertyChangedEventArgs(property));
        }
        public event PropertyChangedEventHandler PropertyChanged;

        public MyEnum Value
        {
            get => Obj.Value;
            set
            {
                if (value != Obj.Value) // Crash happens here because Obj is null
                {
                    Obj.Value = value;
                    OnPropertyChanged(nameof(Value));
                }
            }
        }

        public static IEnumerable<MyEnum> SelectableValues { get; } = new[] { MyEnum.One, MyEnum.Two };

        internal MyObj Obj;

        internal TestModel(MyObj obj)
        {
            Obj = obj;
        }

        public void Dispose()
        {
            Obj = null;
            PropertyChanged = null;
        }
    }